Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 46
Filtrar
Mais filtros

Base de dados
Tipo de documento
Intervalo de ano de publicação
1.
Am J Perinatol ; 2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-37967871

RESUMO

OBJECTIVE: To review the decision aids currently available or being developed to predict a patient's odds that their external cephalic version (ECV) will be successful. STUDY DESIGN: We searched PubMed/MEDLINE, Cochrane Central, and ClinicalTrials.gov from 2015 to 2022. Articles from a pre-2015 systematic review were also included. We selected English-language articles describing or evaluating models (prediction rules) designed to predict an outcome of ECV for an individual patient. Acceptable model outcomes included cephalic presentation after the ECV attempt and whether the ECV ultimately resulted in a vaginal delivery. Two authors independently performed article selection following PRISMA 2020 guidelines. Since 2015, 380 unique records underwent title and abstract screening, and 49 reports underwent full-text review. Ultimately, 17 new articles and 8 from the prior review were included. Of the 25 articles, 22 proposed one to two models each for a total of 25 models, while the remaining 3 articles validated prior models without proposing new ones. RESULTS: Of the 17 new articles, 10 were low, 6 moderate, and 1 high risk of bias. Almost all articles were from Europe (11/25) or Asia (10/25); only one study in the last 20 years was from the United States. The models found had diverse presentations including score charts, decision trees (flowcharts), and equations. The majority (13/25) had no form of validation and only 5/25 reached external validation. Only the Newman-Peacock model (United States, 1993) was repeatedly externally validated (Pakistan, 2012 and Portugal, 2018). Most models (14/25) were published in the last 5 years. In general, newer models were designed more robustly, used larger sample sizes, and were more mathematically rigorous. Thus, although they await further validation, there is great potential for these models to be more predictive than the Newman-Peacock model. CONCLUSION: Only the Newman-Peacock model is ready for regular clinical use. Many newer models are promising but require further validation. KEY POINTS: · 25 ECV prediction models have been published; 14 were in the last 5 years.. · The Newman-Peacock model is currently the only one with sufficient validation for clinical use.. · Many newer models appear to perform better but await further validation..

2.
Behav Sci Law ; 42(4): 417-434, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38769070

RESUMO

Social learning theory has been widely implemented to understand cyber deviance. Nevertheless, the antecedent scholarship homogenously nested in the perspective of offending specification, leaving the offending versatility thesis unattained. The lack of such studies may undermine the capability of comprehensively understanding the social learning patterns of online offending. Using a sample of 3741 Chinese college students, this study estimated an array of binary logistic regressions to compare the effects of traditional and online social learning in four types of online offending (online sexual harassment, cyberbullying, hacking, and digital piracy). The results suggest that offending versatility and offending specification co-exist in the social learning process of cyber deviance, while offending specification explains a marginally greater variance. Besides, online learning variables act as potential mediators in the relationships between traditional learning and cyber deviance. Furthermore, traditional social learning shows greater predictive power in cyber-enabled crimes than in cyber-dependent crimes. Our study provides fresh empirical evidence for the non-exclusive association between offending versatility and offending specification in the social learning process of cyber deviance.


Assuntos
Cyberbullying , Aprendizado Social , Estudantes , Humanos , Feminino , Masculino , Adulto Jovem , Estudantes/psicologia , Cyberbullying/psicologia , Crime/psicologia , Adolescente , Adulto , Criminosos/psicologia , China , Internet , Universidades
3.
J Clin Nurs ; 2024 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-39449184

RESUMO

AIMS: To develop and preliminarily validate a measure of beliefs about compassion in health care and assess whether and which beliefs may predict compassion. DESIGN: Pre-registered cross-sectional online survey study with a repeated-measures vignette component. METHOD: Exploratory and Confirmatory Factor analyses were performed on a split sample of 890 healthcare professionals in Aotearoa New Zealand (NZ). Links with fears of compassion for others, burnout, trait compassion, compassion competency and ability and self-efficacy were used to assess convergent and divergent validity. Linear mixed model regression analyses were used to assess relationships between beliefs and compassion. In writing this report, we adhered to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines. RESULTS: Four-factor structure featuring three negative (compassion as harmful, not useful, draining) and one positive (compassion is important) type of beliefs was established. Confirmatory factor analysis indicated a good fit and subscales indicated good measures of validity. Internal consistency was achieved for the subset of beliefs (harmful, not useful). Regression analyses indicated negative effects of the belief that compassion is draining on caring, motivation to help and compassion overall; negative effects of the belief that compassion is not useful on the motivation to help and a positive effect of the belief that compassion is important on caring and compassion overall. There was no effect of beliefs that compassion is harmful on compassion measures. CONCLUSION: This report extends prior qualitative studies of beliefs about compassion in a large healthcare sample, offering a way to measure these potentially malleable factors that might be targeted in education, interventions and future research. PATIENT OR PUBLIC CONTRIBUTION: The study was designed in consultation with healthcare and compassion research professionals, including substantial input from Indigenous Maori healthcare professionals.

4.
Int J Mol Sci ; 25(14)2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39063127

RESUMO

The production of nanoparticles has recently surged due to their varied applications in the biomedical, pharmaceutical, textile, and electronic sectors. However, this rapid increase in nanoparticle manufacturing has raised concerns about environmental pollution, particularly its potential adverse effects on human health. Among the various concerns, inhalation exposure to nanoparticles poses significant risks, especially affecting the respiratory system. Airway epithelial cells play a crucial role as the primary defense against inhaled particulate matter and pathogens. Studies have shown that nanoparticles can disrupt the airway epithelial barrier, triggering inflammatory responses, generating reactive oxygen species, and compromising cell viability. However, our understanding of how different types of nanoparticles specifically impact the airway epithelial barrier remains limited. Both in vitro cell culture and in vivo murine models are commonly utilized to investigate nanoparticle-induced cellular responses and barrier dysfunction. This review discusses the methodologies frequently employed to assess nanoparticle toxicity and barrier disruption. Furthermore, we analyze and compare the distinct effects of various nanoparticle types on the airway epithelial barrier. By elucidating the diverse responses elicited by different nanoparticles, we aim to provide insights that can guide future research endeavors in assessing and mitigating the potential risks associated with nanoparticle exposure.


Assuntos
Células Epiteliais , Nanopartículas , Humanos , Animais , Nanopartículas/toxicidade , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Mucosa Respiratória/efeitos dos fármacos , Mucosa Respiratória/metabolismo , Mucosa Respiratória/patologia , Testes de Toxicidade/métodos , Espécies Reativas de Oxigênio/metabolismo
5.
J Plan Lit ; 39(1): 25-35, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38332804

RESUMO

Play has well-established physical and mental benefits for people of all ages. Urban spaces, such as parks, provide important public arenas in which to play. But to what extent do planners or planning scholarship focus on facilitating play? Our systematic literature review of 3,800 articles in nineteen academic planning journals returned 126 articles related to play. We found that the planning for play literature is an emerging discourse overwhelmingly focused on children and the physical design of urban spaces in predominantly English-speaking nations. The study identifies gaps in the planning for play literature and outlines recommendations for future research.

6.
Policy Polit Nurs Pract ; 25(4): 228-240, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39262401

RESUMO

The aim of this qualitative evidence synthesis (QES) is to critically appraise the contemporary literature to gain a comprehensive understanding of the barriers and enablers of workplace integration needs of internationally educated nurses (IENs). An electronic search was conducted across multiple databases, and eligibility criteria were applied to identify papers published between January 2013 and July 2023. Out of the 830 studies initially retrieved, six met the inclusion criteria. Study quality was assessed using the Critical Appraisal Skills Programme (CASP) tool. Thematic analysis of the included studies revealed various barriers and enablers for workplace integration experienced by IENs. Barriers were: (a) IEN-related factors (cultural differences, language barriers, and disparities in the scope of nursing practice), (b) organizational factors (poor leadership), and (c) contextual factors (racism and discrimination). Enablers emerged were: (a) IEN-related factors (commitment to learn and adapt) and (b) organizational factors (structured multifaceted program, supportive workplace environment, and mentorship). Dynamic interaction exists among these factors, therefore interventions should address multiple barriers simultaneously. The QES has illuminated essential factors which impact the integration of IENs, and emphasizes the necessity of a comprehensive approach that considers the diverse challenges and opportunities that arise.


Assuntos
Enfermeiros Internacionais , Pesquisa Qualitativa , Local de Trabalho , Humanos , Local de Trabalho/psicologia , Enfermeiros Internacionais/psicologia , Feminino , Masculino , Adulto , Pessoa de Meia-Idade
7.
BMC Pediatr ; 23(1): 181, 2023 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-37072740

RESUMO

OBJECTIVES: To describe children hospitalized with community-acquired pneumonia complicated by effusion (cCAP). DESIGN: Retrospective cohort study. SETTING: A Canadian children's hospital. PARTICIPANTS: Children without significant medical comorbidities aged < 18 years admitted from January 2015-December 2019 to either the Paediatric Medicine or Paediatric General Surgery services with any pneumonia discharge code who were documented to have an effusion/empyaema using ultrasound. OUTCOME MEASURES: Length of stay; admission to the paediatric intensive care unit; microbiologic diagnosis; antibiotic use. RESULTS: There were 109 children without significant medical comorbidities hospitalized for confirmed cCAP during the study period. Their median length of stay was 9 days (Q1-Q3 6-11 days) and 35/109 (32%) were admitted to the paediatric intensive care unit. Most (89/109, 74%) underwent procedural drainage. Length of stay was not associated with effusion size but was associated with time to drainage (0.60 days longer stay per day delay in drainage, 95%CI 0.19-1.0 days). Microbiologic diagnosis was more often made via molecular testing of pleural fluids (43/59, 73%) than via blood culture (12/109, 11%); the main aetiologic pathogens were S. pneumoniae (40/109, 37%), S. pyogenes (15/109, 14%), and S. aureus (7/109, 6%). Discharge on a narrow spectrum antibiotic (i.e. amoxicillin) was much more common when the cCAP pathogen was identified as compared to when it was not (68% vs. 24%, p < 0.001). CONCLUSIONS: Children with cCAP were commonly hospitalized for prolonged periods. Prompt procedural drainage was associated with shorter hospital stays. Pleural fluid testing often facilitated microbiologic diagnosis, which itself was associated with more appropriate antibiotic therapy.


Assuntos
Infecções Comunitárias Adquiridas , Derrame Pleural , Pneumonia , Criança , Humanos , Lactente , Estudos Retrospectivos , Staphylococcus aureus , Canadá , Pneumonia/complicações , Pneumonia/diagnóstico , Pneumonia/tratamento farmacológico , Streptococcus pneumoniae , Antibacterianos/uso terapêutico , Infecções Comunitárias Adquiridas/complicações , Infecções Comunitárias Adquiridas/diagnóstico , Streptococcus pyogenes , Derrame Pleural/diagnóstico , Derrame Pleural/etiologia , Derrame Pleural/terapia
8.
FASEB J ; 34(5): 6166-6184, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32167209

RESUMO

Cancer metastasis and secondary tumor initiation largely depend on circulating tumor cell (CTC) and vascular endothelial cell (EC) interactions by incompletely understood mechanisms. Endothelial glycocalyx (GCX) dysfunction may play a significant role in this process. GCX structure depends on vascular flow patterns, which are irregular in tumor environments. This work presents evidence that disturbed flow (DF) induces GCX degradation, leading to CTC homing to the endothelium, a first step in secondary tumor formation. A 2-fold greater attachment of CTCs to human ECs was found to occur under DF conditions, compared to uniform flow (UF) conditions. These results corresponded to an approximately 50% decrease in wheat germ agglutinin (WGA)-labeled components of the GCX under DF conditions, vs UF conditions, with undifferentiated levels of CTC-recruiting E-selectin under DF vs UF conditions. Confirming the role of the GCX, neuraminidase induced the degradation of WGA-labeled GCX under UF cell culture conditions or in Balb/C mice and led to an over 2-fold increase in CTC attachment to ECs or Balb/C mouse lungs, respectively, compared to untreated conditions. These experiments confirm that flow-induced GCX degradation can enable metastatic CTC arrest. This work, therefore, provides new insight into pathways of secondary tumor formation.


Assuntos
Neoplasias da Mama/patologia , Endotélio Vascular/patologia , Glicocálix/metabolismo , Hemodinâmica , Neoplasias Pulmonares/secundário , Células Neoplásicas Circulantes/patologia , Neuraminidase/metabolismo , Animais , Neoplasias da Mama/metabolismo , Células Cultivadas , Selectina E/metabolismo , Endotélio Vascular/metabolismo , Feminino , Humanos , Neoplasias Pulmonares/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Células Neoplásicas Circulantes/metabolismo
9.
Gastroenterology ; 154(3): 585-598, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29031501

RESUMO

BACKGROUND & AIMS: We analyzed DNA methylation patterns and transcriptomes of primary intestinal epithelial cells (IEC) of children newly diagnosed with inflammatory bowel diseases (IBD) to learn more about pathogenesis. METHODS: We obtained mucosal biopsies (N = 236) collected from terminal ileum and ascending and sigmoid colons of children (median age 13 years) newly diagnosed with IBD (43 with Crohn's disease [CD], 23 with ulcerative colitis [UC]), and 30 children without IBD (controls). Patients were recruited and managed at a hospital in the United Kingdom from 2013 through 2016. We also obtained biopsies collected at later stages from a subset of patients. IECs were purified and analyzed for genome-wide DNA methylation patterns and gene expression profiles. Adjacent microbiota were isolated from biopsies and analyzed by 16S gene sequencing. We generated intestinal organoid cultures from a subset of samples and genome-wide DNA methylation analysis was performed. RESULTS: We found gut segment-specific differences in DNA methylation and transcription profiles of IECs from children with IBD vs controls; some were independent of mucosal inflammation. Changes in gut microbiota between IBD and control groups were not as large and were difficult to assess because of large amounts of intra-individual variation. Only IECs from patients with CD had changes in DNA methylation and transcription patterns in terminal ileum epithelium, compared with controls. Colon epithelium from patients with CD and from patients with ulcerative colitis had distinct changes in DNA methylation and transcription patterns, compared with controls. In IECs from patients with IBD, changes in DNA methylation, compared with controls, were stable over time and were partially retained in ex-vivo organoid cultures. Statistical analyses of epithelial cell profiles allowed us to distinguish children with CD or UC from controls; profiles correlated with disease outcome parameters, such as the requirement for treatment with biologic agents. CONCLUSIONS: We identified specific changes in DNA methylation and transcriptome patterns in IECs from pediatric patients with IBD compared with controls. These data indicate that IECs undergo changes during IBD development and could be involved in pathogenesis. Further analyses of primary IECs from patients with IBD could improve our understanding of the large variations in disease progression and outcomes.


Assuntos
Colite Ulcerativa/genética , Colo Sigmoide/metabolismo , Doença de Crohn/genética , Metilação de DNA , Epigênese Genética , Células Epiteliais/metabolismo , Íleo/metabolismo , Mucosa Intestinal/metabolismo , Transcrição Gênica , Transcriptoma , Adolescente , Fatores Etários , Biópsia , Estudos de Casos e Controles , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/microbiologia , Colo Sigmoide/microbiologia , Doença de Crohn/diagnóstico , Doença de Crohn/microbiologia , Diagnóstico Diferencial , Inglaterra , Células Epiteliais/microbiologia , Feminino , Microbioma Gastrointestinal , Perfilação da Expressão Gênica/métodos , Estudo de Associação Genômica Ampla , Humanos , Íleo/microbiologia , Mucosa Intestinal/microbiologia , Masculino , Organoides , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Ribotipagem , Fatores de Tempo , Técnicas de Cultura de Tecidos
10.
Cureus ; 16(2): e54683, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38523969

RESUMO

Recurrent painful ophthalmoplegic neuropathy (RPON), previously known as ophthalmoplegic migraine, is a disorder typically characterized by recurrent episodes of unilateral headache concurrent with ipsilateral ocular cranial nerve paresis which primarily affects children. Diagnosis is mostly one of exclusion, based on clinical symptoms, supplemented by imaging for enhanced or distorted oculomotor nerves. We present a case of RPON in a 24-year-old adult female with unique features of unilateral left headache with ipsilateral pupillary dilation spreading to bilateral dilation and no MRI findings of oculomotor nerve enhancement.

11.
Tissue Barriers ; : 2300579, 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38166590

RESUMO

Titanium dioxide fine particles (TiO2-FPs) and nanoparticles (TiO2-NPs) are the most widely used whitening pigments worldwide. Inhalation of TiO2-FPs and TiO2-NPs can be harmful as it triggers toxicity in the airway epithelial cells. The airway epithelium serves as the respiratory system's first line of defense in which airway epithelial cells are significant targets of inhaled pathogens and environmental particles. Our group previously found that TiO2-NPs lead to a disrupted barrier in the polarized airway epithelial cells. However, the effect of TiO2-FPs on the respiratory epithelial barrier has not been examined closely. In this study, we aimed to compare the effects of TiO2-FPs and TiO2-NPs on the structure and function of the airway epithelial barrier. Additionally, we hypothesized that 8-Bromo-cAMP, a cyclic adenosine monophosphate (cAMP) derivative, would alleviate the disruptive effects of both TiO2-FPs and TiO2-NPs. We observed increased epithelial membrane permeability in both TiO2-FPs and TiO2-NPs after exposure to 16HBE cells. Immunofluorescent labeling showed that both particle sizes disrupted the structural integrity of airway epithelial tight junctions and adherens junctions. TiO2-FPs had a slightly more, but insignificant impact on the epithelial barrier disruption than TiO2-NPs. Treatment with 8-Bromo-cAMP significantly attenuated the barrier-disrupting impact of both TiO2-FPs and TiO2-NPs on cell monolayers. Our study demonstrates that both TiO2-FPs and TiO2-NPs cause comparable barrier disruption and suggests a protective role for cAMP signaling. The observed effects of TiO2-FPs and TiO2-NPs provide a necessary understanding for characterizing the pathways involved in the defensive role of the cAMP pathway on TiO2-induced airway barrier disruption.

12.
medRxiv ; 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38464022

RESUMO

We explored blockchain's applications in nursing informatics, highlighting its potential to improve patient care and data management. We compared and analyzed eight studies focusing on blockchain in Electronic Health Records (EHR) management, nursing optimization, and research facilitation. Although most of these studies are in the proposal stage, blockchain's technical features show promise in enhancing nursing practices and supporting nursing informatics researchers with the integration of technologies.

13.
PLoS One ; 19(8): e0308102, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39208211

RESUMO

BACKGROUND: The main mode of transmission of Hepatitis C in North America is through injection drug use. Availability of accessible care for people who inject drugs is crucial for achieving hepatitis C elimination. OBJECTIVE: The objective of this analysis is to compare the changes in injection drug use frequency and high-risk injection behaviors in participants who were randomized to accessible hepatitis c care versus usual hepatitis c care. METHODS: Participants who were hepatitis C virus RNA positive and had injected drugs in the last 90 days were enrolled and randomized 1:1 to an on-site, low threshold accessible care arm or a standard, referral-based usual care arm. Participants attended follow-up appointments at 3, 6, 9, and 12 months during which they answered questions regarding injection drug use frequency, behaviors, and treatment for opioid use disorder. PRIMARY OUTCOMES: The primary outcomes of this secondary analysis are the changes in the frequency of injection drug use, high-risk injection behaviors, and receiving medication for opioid use disorder in the last 30 days. RESULTS: A total of 165 participants were enrolled in the study, with 82 participants in the accessible care arm and 83 participants in the usual care arm. Participants in the accessible care arm were found to have a statistically significant higher likelihood of reporting a lower range of injection days (accessible care-by-time effect OR = 0.78, 95% CI = 0.62-0.98) and injection events (accessible care-by-time effect OR = 0.70, 95% CI = 0.56-0.88) in the last 30 days at a follow-up interview relative to those in the usual care arm. There were no statistically significant differences in the rates of decrease in receptive sharing of injection equipment or in the percentage of participants receiving treatment for opioid use disorders in the two arms. CONCLUSION: Hepatitis C treatment through an accessible care model resulted in statistically higher rates of decrease in injection drug use frequency in people who inject drugs.


Assuntos
Hepatite C , Programas de Troca de Agulhas , Abuso de Substâncias por Via Intravenosa , Humanos , Masculino , Feminino , Hepatite C/tratamento farmacológico , Hepatite C/epidemiologia , Abuso de Substâncias por Via Intravenosa/complicações , Adulto , Pessoa de Meia-Idade , Assunção de Riscos , Transtornos Relacionados ao Uso de Opioides/terapia , Transtornos Relacionados ao Uso de Opioides/epidemiologia
14.
Sci Rep ; 14(1): 25178, 2024 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-39448747

RESUMO

Recent progress in deep learning has significantly impacted materials science, leading to accelerated material discovery and innovation. ElemNet, a deep neural network model that predicts formation energy from elemental compositions, exemplifies the application of deep learning techniques in this field. However, the "black-box" nature of deep learning models often raises concerns about their interpretability and reliability. In this study, we propose XElemNet to explore the interpretability of ElemNet by applying a series of explainable artificial intelligence (XAI) techniques, focusing on post-hoc analysis and model transparency. The experiments with artificial binary datasets reveal ElemNet's effectiveness in predicting convex hulls of element-pair systems across periodic table groups, indicating its capability to effectively discern elemental interactions in most cases. Additionally, feature importance analysis within ElemNet highlights alignment with chemical properties of elements such as reactivity and electronegativity. XElemNet provides insights into the strengths and limitations of ElemNet and offers a potential pathway for explaining other deep learning models in materials science.

15.
NPJ Precis Oncol ; 8(1): 47, 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38396241

RESUMO

Malignant pleural mesothelioma (MPM) is a rare but lethal pleural cancer with high intratumor heterogeneity (ITH). A recent study in lung adenocarcinoma has developed a clonal gene signature (ORACLE) from multiregional transcriptomic data and demonstrated high prognostic values and reproducibility. However, such a strategy has not been tested in other types of cancer with high ITH. We aimed to identify biomarkers from multi-regional data to prognostically stratify MPM patients. We generated a multiregional RNA-seq dataset for 78 tumor samples obtained from 26 MPM patients, each with one sample collected from a superior, lateral, and inferior region of the tumor. By integrating this dataset with the Cancer Genome Atlas MPM RNA-seq data, we selected 29 prognostic genes displaying high variability across different tumors but low ITH, which named PRACME (Prognostic Risk Associated Clonal Mesothelioma Expression). We evaluated PRACME in two independent MPM datasets and demonstrated its prognostic values. Patients with high signature scores are associated with poor prognosis after adjusting established clinical factors. Interestingly, the PRACME and the ORACLE signatures defined respectively from MPM and lung adenocarcinoma cross-predict prognosis between the two cancer types. Further investigation indicated that the cross-prediction ability might be explained by the high similarity between the two cancer types in their genomic regions with copy number variation, which host many clonal genes. Overall, our clonal signature PRACME provided prognostic stratification in MPM and this study emphasized the importance of multi-regional transcriptomic data for prognostic stratification based on clonal genes.

16.
Artigo em Inglês | MEDLINE | ID: mdl-39395787

RESUMO

OBJECTIVE: Immune checkpoint therapy (ICT) has significantly impacted malignant pleural mesothelioma (MPM) treatment. Despite some promising results from combination therapies, nearly half of MPM patients do not benefit, underscoring the urgent need for reliable predictive biomarkers. This study assesses the prognostic value of serum soluble mesothelin-related peptide (SMRP) and PD-L1 levels in MPM patients receiving ICT. METHODS: We conducted a retrospective analysis of 125 MPM patients treated with ICT by measuring pre-ICT serum levels of SMRP and PD-L1. We also examined the correlation of these serum levels with tumor mRNA expressions of MSLN and PD-L1. Both univariable and multivariable Cox regression analyses were used to determine independent prognosticators for overall survival (OS). A prospective ICT clinical trial and our historical cohort were included for validation. RESULTS: Seventy-seven patients (62%) were treated with either anti-PD-(L)1 monotherapy, and the remaining 38% were given combination ICT. Higher pre-ICT SMRP levels were observed in epithelioid versus non-epithelioid MPM. Serum PD-L1 levels did not show significant differences between the groups. Univariable analysis identified durable clinical benefit, development of immune-related adverse events, and SMRP levels as significantly associated with OS. Multivariable analysis confirmed SMRP as an independent prognostic factor, with lower levels (≤1.35 nmol/L) correlating with improved OS. The association of high SMRP with worse prognosis was validated in the prospective ICT clinical trial cohort and not in our historical cohort treated without ICT. CONCLUSIONS: SMRP is a promising serum biomarker for predicting survival in MPM patients treated with ICT and warrants prospective investigation.

17.
Paediatr Child Health ; 22(1): 39-40, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29479173
18.
Front Sociol ; 7: 876070, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35663603

RESUMO

The transfer of power stemming from the 2020 presidential election occurred during an unprecedented period in United States history. Uncertainty from the COVID-19 pandemic, ongoing societal tensions, and a fragile economy increased societal polarization, exacerbated by the outgoing president's offline rhetoric. As a result, online groups such as QAnon engaged in extra political participation beyond the traditional platforms. This research explores the link between offline political speech and online extra-representational participation by examining Twitter within the context of the January 6 insurrection. Using a mixed-methods approach of quantitative and qualitative thematic analyses, the study combines offline speech information with Twitter data during key speech addresses leading up to the date of the insurrection; exploring the link between Trump's offline speeches and QAnon's hashtags across a 3-day timeframe. We find that links between online extra-representational participation and offline political speech exist. This research illuminates this phenomenon and offers policy implications for the role of online messaging as a tool of political mobilization.

19.
Lab Chip ; 22(23): 4603-4620, 2022 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-36326069

RESUMO

Blood-brain barrier (BBB) endothelial cell (EC) function depends on flow conditions and on supportive cells, like pericytes and astrocytes, which have been shown to be both beneficial and detrimental for brain EC function. Most studies investigating BBB EC function lack physiological relevance, using sub-physiological shear stress magnitudes and/or omitting pericytes and astrocytes. In this study, we developed a millifluidic device compatible with standard transwell inserts to investigate BBB function. In contrast to standard polydimethylsiloxane (PDMS) microfluidic devices, this model allows for easy, reproducible shear stress exposure without common limitations of PDMS devices such as inadequate nutrient diffusion and air bubble formation. In no-flow conditions, we first used the device to examine the impact of primary human pericytes and astrocytes on human brain microvascular EC (HBMEC) barrier integrity. Astrocytes, pericytes, and a 1-to-1 ratio of both cell types increased HBMEC barrier integrity via reduced 3 and 40 kDa fluorescent dextran permeability and increased claudin-5 expression. There were differing levels of low 3 kDa permeability in HBMEC-pericyte, HBMEC-astrocyte, and HBMEC-astrocyte-pericyte co-cultures, while levels of low 40 kDa permeability were consistent across co-cultures. The 3 kDa findings suggest that pericytes provide more barrier support to the BBB model compared to astrocytes, although both supportive cell types are permeability reducers. Incorporation of 24-hour 12 dynes per cm2 flow significantly reduced dextran permeability in HBMEC monolayers, but not in the tri-culture model. These results indicate that tri-culture may exert more pronounced impact on overall BBB permeability than flow exposure. In both cases, monolayer and tri-culture, flow exposure interestingly reduced HBMEC expression of both claudin-5 and occludin. ZO-1 expression, and localization at cell-cell junctions increased in the tri-culture but exhibited no apparent change in the HBMEC monolayer. Under flow conditions, we also observed HBMEC alignment in the tri-culture but not in HBMEC monolayers, indicating supportive cells and flow are both essential to observe brain EC alignment in vitro. Collectively, these results support the necessity of physiologically relevant, multicellular BBB models when investigating BBB EC function. Consideration of the roles of shear stress and supportive cells within the BBB is critical for elucidating the physiology of the neurovascular unit.


Assuntos
Barreira Hematoencefálica , Dextranos , Humanos , Claudina-5/metabolismo , Pericitos/metabolismo , Astrócitos , Técnicas de Cocultura , Células Cultivadas
20.
BMJ Open ; 11(12): e052593, 2021 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-34857570

RESUMO

In the UK, over 20% of patients leaving hospital after a stroke will be severely disabled. Despite this, limited clinical guidance is available to teams tasked with providing support for this complex population at home. Additionally, many areas across the UK are not commissioned to treat this patient cohort, leaving them with no specialist support on discharge. OBJECTIVES: To establish core components of home-based rehabilitation for survivors of stroke with severe disability, based on expert panel consensus. SETTING: Virtual nominal group technique (vNGT) across the UK. PARTICIPANTS: Experts in the field of stroke rehabilitation (n=14) including researchers, clinicians and those with lived experience. METHODS: Two vNGT were completed using a freely available online platform, Microsoft Teams. The technique's five stages were completed virtually; introduction, silent idea generation, round robin, clarifications and scoring. Statements were analysed for consensus, those achieving consensus underwent content analysis to form rich overarching consensus statements. RESULTS: A combined total of 421 statements achieved positive consensus (>75% in agreement), which formed 11 overarching consensus statements. These outline key components of home-based rehabilitation for survivors of stroke with severe disability including the structure and members of the team, as well as the skills and knowledge required. CONCLUSION: The consensus statements highlight the complexity of managing patients with severe stroke disability following discharge from hospital. This study has the potential to support the provision of services for this patient group, providing a benchmark for commissioners and clinicians as well as setting expectations for stroke survivors and their carers. What remains unknown is how many services currently offer this service to patients with severe disability.


Assuntos
Pessoas com Deficiência , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Humanos , Alta do Paciente , Sobreviventes
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA