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1.
J Am Pharm Assoc (2003) ; : 102190, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39032865

RESUMO

OBJECTIVE: The objective of this quality assurance initiative was to internally measure children's perceptions of the book, "All Aboard the Rx-Express!" and knowledge gained from its content. METHODS: This pharmacy-focused children's book was read to elementary-age youth at a rural, Pennsylvania elementary school in the Spring of 2022. A brief, optional, anonymous pre-post survey was administered to the youth before and after the reading to measure the book's impact on third through fifth graders' perceptions and knowledge of the pharmacy profession. Descriptive statistics, chi squared analysis, independent samples t-tests, and one sample proportions tests were used to analyze survey responses. RESULTS: One hundred ninety-one students participated in the pre-survey to assess baseline knowledge about the pharmacy profession before the book was read. One hundred eighty-five students answered the post-survey. Pre-post respondent demographics were collected in aggregate and were not significantly different between the pre- and post-cohorts. Survey results demonstrated an increase in all questions that asked about students' perceptions of pharmacists and the profession, and students reported favorable perceptions of the book itself. CONCLUSION: Early interventions such as this can increase elementary-age youth's perceptions and knowledge of the roles of pharmacists. Future work in early intervention will be needed to increase interest in the profession and admissions to pharmacy schools.

2.
Brief Bioinform ; 22(2): 946-962, 2021 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-33078827

RESUMO

Given the scale and rapid spread of the coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, or 2019-nCoV), there is an urgent need to identify therapeutics that are effective against COVID-19 before vaccines are available. Since the current rate of SARS-CoV-2 knowledge acquisition via traditional research methods is not sufficient to match the rapid spread of the virus, novel strategies of drug discovery for SARS-CoV-2 infection are required. Structure-based virtual screening for example relies primarily on docking scores and does not take the importance of key residues into consideration, which may lead to a significantly higher incidence rate of false-positive results. Our novel in silico approach, which overcomes these limitations, can be utilized to quickly evaluate FDA-approved drugs for repurposing and combination, as well as designing new chemical agents with therapeutic potential for COVID-19. As a result, anti-HIV or antiviral drugs (lopinavir, tenofovir disoproxil, fosamprenavir and ganciclovir), antiflu drugs (peramivir and zanamivir) and an anti-HCV drug (sofosbuvir) are predicted to bind to 3CLPro in SARS-CoV-2 with therapeutic potential for COVID-19 infection by our new protocol. In addition, we also propose three antidiabetic drugs (acarbose, glyburide and tolazamide) for the potential treatment of COVID-19. Finally, we apply our new virus chemogenomics knowledgebase platform with the integrated machine-learning computing algorithms to identify the potential drug combinations (e.g. remdesivir+chloroquine), which are congruent with ongoing clinical trials. In addition, another 10 compounds from CAS COVID-19 antiviral candidate compounds dataset are also suggested by Molecular Complex Characterizing System with potential treatment for COVID-19. Our work provides a novel strategy for the repurposing and combinations of drugs in the market and for prediction of chemical candidates with anti-COVID-19 potential.


Assuntos
Antivirais/farmacologia , SARS-CoV-2/efeitos dos fármacos , Descoberta de Drogas , Reposicionamento de Medicamentos/métodos , Simulação de Acoplamento Molecular
3.
J Acoust Soc Am ; 152(3): 1932, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36182282

RESUMO

Project-based learning engages students in practical activities related to course content and has been demonstrated to improve academic performance. Due to its reported benefits, this form of active learning was incorporated with an ongoing research project into an introductory, graduate-level Musical Acoustics course at the Peabody Institute of The Johns Hopkins University. Students applied concepts from the course to characterize a contact sensor with a polymer diaphragm for musical instrument recording. Assignments throughout the semester introduced students to completing a literature review, planning an experiment, collecting and analyzing data, and presenting results. While students were given broad goals to understand the performance of the contact sensor compared to traditional microphones, they were allowed independence in determining the specific methods used. The efficacy of the course framework and research project was assessed with student feedback provided through open-ended prompts and Likert-type survey questions. Overall, the students responded positively to the project-based learning and demonstrated mastery of the course learning objectives. The work provides a possible framework for instructors considering using project-based learning through research in their own course designs.


Assuntos
Acústica , Aprendizagem Baseada em Problemas , Retroalimentação , Humanos
4.
Adv Funct Mater ; 30(48)2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33551712

RESUMO

Cell-free small diameter vascular grafts, based on small intestinal submucosa (SIS) functionalized with heparin and vascular endothelial growth factor (VEGF) manufactured and implanted successfully into the arterial system of neonatal lambs, where they remained patent and grew in size with the host to a similar extent and with similar rate as native arteries. Acellular tissue engineered vessels (A-TEV) integrated seamlessly into the native vasculature and developed confluent, functional endothelium that afforded patency. The medial layer was infiltrated by smooth muscle cells, showed no signs of calcification and developed contractile function. The vascular wall underwent remarkable extracellular matrix remodeling exhibiting elastin fibers and even inner elastic lamina within six months. Taken together, our results suggest that VEGF-based A-TEVs may be suitable for treatment of congenital heart disorders to alleviate the need for repeated surgeries, which are currently standard practice.

5.
FASEB J ; 33(4): 5089-5100, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30629890

RESUMO

Recently, our group demonstrated that immobilized VEGF can capture flowing endothelial cells (ECs) from the blood in vitro and promote endothelialization and patency of acellular tissue-engineered vessels (A-TEVs) into the arterial system of an ovine animal model. Here, we demonstrate implantability of submillimeter diameter heparin and VEGF-decorated A-TEVs in a mouse model and discuss the cellular and immunologic response. At 1 mo postimplantation, the graft lumen was fully endothelialized, as shown by expression of EC markers such as CD144, eNOS, CD31, and VEGFR2. Interestingly, the same cells coexpressed leukocyte/macrophage (Mϕ) markers CD14, CD16, VEGFR1, CD38, and EGR2. Notably, there was a stark difference in the cellular makeup between grafts containing VEGF and those containing heparin alone. In VEGF-containing grafts, infiltrating monocytes (MCs) converted into anti-inflammatory M2-Mϕs, and the grafts developed well-demarcated luminal and medial layers resembling those of native arteries. In contrast, in grafts containing only heparin, MCs converted primarily into M1-Mϕs, and the endothelial and smooth muscle layers were not well defined. Our results indicate that VEGF may play an important role in regulating A-TEV patency and regeneration, possibly by regulating the inflammatory response to the implants.-Smith, R. J., Jr., Yi, T., Nasiri, B., Breuer, C. K., Andreadis, S. T. Implantation of VEGF-functionalized cell-free vascular grafts: regenerative and immunological response.


Assuntos
Macrófagos/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Animais , Endotélio/metabolismo , Feminino , Imuno-Histoquímica , Camundongos , Camundongos Endogâmicos C57BL , Monócitos/metabolismo
6.
Clin Transplant ; 32(5): e13235, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29517815

RESUMO

A systematic review of papers in English on post-transplant lymphoproliferative disorder (PTLD) in lung transplant recipients (LTR) using MEDLINE, EMBASE, SCOPUS, and Cochrane databases was performed. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations were strictly adhered to. Pooled odds ratios (pOR) were calculated from a random-effects model, and heterogeneity among studies was quantitated using I2 values. Fourteen studies published from 2005 to 2015 were included in the meta-analysis. One hundred and sixty-four lung transplant recipients were included. LTRs who received single vs bilateral were associated with a 7.67-fold risk of death after PTLD (6 studies with 64 LTRs; pOR 7.67 95% CI 1.98-29.70; P = .003). pOR of death for early onset PTLD (<1 year post-LT) vs late onset (>1 year post-LT) was not different (3 studies with 72 LTRS; pOR 0.62, 95% CI 0.20-1.86, P = .39). Standardized mean difference (SMD) in time from transplant to PTLD onset between LTRs who died vs alive was not different (9 studies with 109 LTRs; SMD 0.03, 95% CI -0.48-0.53, P = .92). Survival in polymorphic vs monomorphic PTLD and extranodal vs nodal disease was similar (4 studies with 31 LTRs; pOR 0.44, 95% CI 0.08-2.51; P = .36. 6 studies with 81 LTRs; pOR 1.05 95% CI 0.31-3.52, P = .94). This meta-analysis demonstrates that single LTRs are at a higher risk of death vs bilateral LTRs after the development of PTLD.


Assuntos
Rejeição de Enxerto/etiologia , Pneumopatias/cirurgia , Transplante de Pulmão/efeitos adversos , Transtornos Linfoproliferativos/etiologia , Complicações Pós-Operatórias , Humanos
7.
Ann Pharmacother ; 51(8): 649-655, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28438043

RESUMO

BACKGROUND: Dual antiplatelet therapy is a mainstay of care for percutaneous coronary intervention (PCI) patients; however, uncertainty exists in real-world practice about comparative effectiveness and safety outcomes. OBJECTIVE: To evaluate outcomes of different oral P2Y12 inhibitors in PCI patients. METHODS: We retrospectively studied patients treated between July 1, 2010, and December 31, 2013. Patients received clopidogrel, prasugrel, ticagrelor, or more than 1 antiplatelet (switch) during PCI. Outcomes were evaluated for major adverse cardiovascular events (MACE) and bleeding at 1 year. Propensity score matching with Cox proportional hazards analysis was used to determine predictors of MACE and bleeding. RESULTS: A total of 8127 patients were included: clopidogrel (n = 6872), prasugrel (n = 605), ticagrelor (n = 181), and switch (n = 469). Treatment with prasugrel was associated with the lowest risk of MACE using multivariate regression (odds ratio [OR] = 0.57; 95% CI = 0.36-0.92; P = 0.02). In the propensity score-matched analysis, only the prasugrel group was associated with a lower risk of MACE compared with the clopidogrel group. Clopidogrel was associated with the lowest risk of major bleeding using multivariate regression (OR = 0.64; 95% CI = 0.42-0.98; P = 0.042). Both ticagrelor (hazard ratio [HR] = 2.00; 95% CI = 1.11-3.59) and the switch groups (HR = 1.65; 95% CI = 1.09-2.50) were associated with a greater risk of major bleeding compared with clopidogrel. However, no differences were found in the propensity score-matched analysis. CONCLUSIONS: Dual antiplatelet therapies differed in both MACE and bleeds in a real-world setting of PCI. Prasugrel was associated with fewer MACE, whereas clopidogrel had fewer major bleeding events.


Assuntos
Síndrome Coronariana Aguda/cirurgia , Intervenção Coronária Percutânea , Inibidores da Agregação Plaquetária/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Síndrome Coronariana Aguda/sangue , Adenosina/administração & dosagem , Adenosina/efeitos adversos , Adenosina/análogos & derivados , Adenosina/uso terapêutico , Idoso , Clopidogrel , Prestação Integrada de Cuidados de Saúde , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Inibidores da Agregação Plaquetária/administração & dosagem , Inibidores da Agregação Plaquetária/efeitos adversos , Cloridrato de Prasugrel/administração & dosagem , Cloridrato de Prasugrel/efeitos adversos , Cloridrato de Prasugrel/uso terapêutico , Pontuação de Propensão , Modelos de Riscos Proporcionais , Antagonistas do Receptor Purinérgico P2Y/administração & dosagem , Antagonistas do Receptor Purinérgico P2Y/efeitos adversos , Receptores Purinérgicos P2Y12/metabolismo , Estudos Retrospectivos , Segurança , Ticagrelor , Ticlopidina/administração & dosagem , Ticlopidina/efeitos adversos , Ticlopidina/análogos & derivados , Ticlopidina/uso terapêutico
8.
J Am Pharm Assoc (2003) ; 56(3): 316-22, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27083852

RESUMO

OBJECTIVE: To describe common facilitators, challenges, and lessons learned in 5 schools and colleges of pharmacy in establishing community pharmacy research fellowships. SETTING: Five schools and colleges of pharmacy in the United States. PRACTICE DESCRIPTION: Schools and colleges of pharmacy with existing community partnerships identified a need and ability to develop opportunities for pharmacists to engage in advanced research training. PRACTICE INNOVATION: Community pharmacy fellowships, each structured as 2 years long and in combination with graduate coursework, have been established at the University of Pittsburgh, Purdue University, East Tennessee State University, University of North Carolina at Chapel Hill, and The Ohio State University. EVALUATION: Program directors from each of the 5 community pharmacy research fellowships identified common themes pertaining to program structure, outcomes, and lessons learned to assist others planning similar programs. RESULTS: Common characteristics across the programs include length of training, prerequisites, graduate coursework, mentoring structure, and immersion into a pharmacist patient care practice. Common facilitators have been the existence of strong community pharmacy partnerships, creating a fellowship advisory team, and networking. A common challenge has been recruitment, with many programs experiencing at least one year without filling the fellowship position. All program graduates (n = 4) have been successful in securing pharmacy faculty positions. CONCLUSION: Five schools and colleges of pharmacy share similar experiences in implementing community pharmacy research fellowships. Early outcomes show promise for this training pathway in growing future pharmacist-scientists focused on community pharmacy practice.


Assuntos
Educação de Pós-Graduação em Farmácia/organização & administração , Bolsas de Estudo/organização & administração , Pesquisa em Farmácia/educação , Faculdades de Farmácia/organização & administração , Comportamento Cooperativo , Humanos , Estados Unidos
9.
Toxicol Appl Pharmacol ; 288(2): 240-8, 2015 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-26232187

RESUMO

The no-observed-adverse-effect level (NOAEL) of a drug defined from animal studies is important for inferring a maximal safe dose in human. However, several issues are associated with its concept, determination and application. It is confined to the actual doses used in the study; becomes lower with increasing sample size or dose levels; and reflects the risk level seen in the experiment rather than what may be relevant for human. We explored a pharmacometric approach in an attempt to address these issues. We first used simulation to examine the behaviour of the NOAEL values as determined by current common practice; and then fitted the probability of toxicity as a function of treatment duration and dose to data collected from all applicable toxicology studies of a test compound. Our investigation was in the context of an irreversible toxicity that is detected at the end of the study. Simulations illustrated NOAEL's dependency on experimental factors such as dose and sample size, as well as the underlying uncertainty. Modelling the probability as a continuous function of treatment duration and dose simultaneously to data from multiple studies allowed the estimation of the dose, along with its confidence interval, for a maximal risk level that might be deemed as acceptable for human. The model-based data integration also reconciled between-study inconsistency and explicitly provided maximised estimation confidence. Such alternative NOAEL determination method should be explored for its more efficient data use, more quantifiable insight to toxic doses, and the potential for more relevant animal-to-human translation.


Assuntos
Comportamento Animal/efeitos dos fármacos , Descoberta de Drogas/métodos , Modelos Biológicos , Modelos Estatísticos , Testículo/efeitos dos fármacos , Testes de Toxicidade/métodos , Animais , Simulação por Computador , Relação Dose-Resposta a Droga , Humanos , Masculino , Nível de Efeito Adverso não Observado , Probabilidade , Ratos , Medição de Risco , Especificidade da Espécie , Testículo/patologia , Fatores de Tempo
10.
Am J Ind Med ; 58(5): 494-508, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25675894

RESUMO

BACKGROUND: Airborne fiber size has been shown to be an important factor relative to adverse lung effects of asbestos and suggested in animal studies of carbon nanotubes and nanofibers (CNT/CNF). MATERIALS AND METHODS: The International Standards Organization (ISO) transmission electron microscopy (TEM) method for asbestos was modified to increase the statistical precision of fiber size determinations, improve efficiency, and reduce analysis costs. Comparisons of the fiber size distributions and exposure indices by laboratory and counting method were performed. RESULTS: No significant differences in size distributions by the ISO and modified ISO methods were observed. Small but statistically-significant inter-lab differences in the proportion of fibers in some size bins were found, but these differences had little impact on the summary exposure indices. The modified ISO method produced slightly more precise estimates of the long fiber fraction (>15 µm). CONCLUSIONS: The modified ISO method may be useful for estimating size-specific structure exposures, including CNT/CNF, for risk assessment research.


Assuntos
Poluentes Ocupacionais do Ar/análise , Amianto/análise , Microscopia Eletrônica de Transmissão/métodos , Nanofibras/análise , Nanotubos de Carbono/análise , Exposição Ocupacional/análise , Tamanho da Partícula , Monitoramento Ambiental/métodos , Humanos , Medição de Risco
11.
Public Underst Sci ; 24(5): 563-81, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25605748

RESUMO

We empirically examine the reporting on biotechnology in Kenyan and international newspapers between 2010 and early 2014. We identify news articles that reported on biotechnology and analyze their use of words to determine whether there is a balance in the reporting of perceived risks and benefits. We also consider how the sources used in news articles and how the publication of the Séralini study of rats fed genetically modified maize affect the balance of reporting of perceived risks and benefits. We find that in Kenyan news reporting, more articles mention perceived benefits than risks, but when risks are mentioned, new articles contain more references to risks than to benefits. We also find that sources affect the reporting of perceived risks and benefits and that the Séralini study increased the likelihood that perceived risks are reported in Kenyan news reporting, but not in international newspapers.


Assuntos
Produtos Agrícolas/genética , Alimentos Geneticamente Modificados/efeitos adversos , Disseminação de Informação , Jornalismo , Manihot/genética , Plantas Geneticamente Modificadas/efeitos adversos , Opinião Pública , Quênia , Jornais como Assunto
12.
Cardiovasc Res ; 120(8): 839-854, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38742656

RESUMO

Cell-free tissue-engineered vascular grafts provide a promising alternative to treat cardiovascular disease, but timely endothelialization is essential for ensuring patency and proper functioning post-implantation. Recent studies from our lab showed that blood cells like monocytes (MCs) and macrophages (Mϕ) may contribute directly to cellularization and regeneration of bioengineered arteries in small and large animal models. While MCs and Mϕ are leucocytes that are part of the innate immune response, they share common developmental origins with endothelial cells (ECs) and are known to play crucial roles during vessel formation (angiogenesis) and vessel repair after inflammation/injury. They are highly plastic cells that polarize into pro-inflammatory and anti-inflammatory phenotypes upon exposure to cytokines and differentiate into other cell types, including EC-like cells, in the presence of appropriate chemical and mechanical stimuli. This review focuses on the developmental origins of MCs and ECs; the role of MCs and Mϕ in vessel repair/regeneration during inflammation/injury; and the role of chemical signalling and mechanical forces in Mϕ inflammation that mediates vascular graft regeneration. We postulate that comprehensive understanding of these mechanisms will better inform the development of strategies to coax MCs/Mϕ into endothelializing the lumen and regenerate the smooth muscle layers of cell-free bioengineered arteries and veins that are designed to treat cardiovascular diseases and perhaps the native vasculature as well.


Assuntos
Prótese Vascular , Macrófagos , Monócitos , Regeneração , Engenharia Tecidual , Humanos , Monócitos/metabolismo , Monócitos/transplante , Engenharia Tecidual/métodos , Animais , Macrófagos/metabolismo , Neovascularização Fisiológica , Fenótipo , Implante de Prótese Vascular/instrumentação , Implante de Prótese Vascular/efeitos adversos , Células Endoteliais/metabolismo , Células Endoteliais/transplante , Desenho de Prótese , Mecanotransdução Celular
13.
Artigo em Inglês | MEDLINE | ID: mdl-39019152

RESUMO

OBJECTIVE: Lung cancer remains a major cause of mortality worldwide, necessitating further understanding of carcinogenesis and its driving factors, including those impacted by sex-dependent variables. We hypothesized that sex-specific lung immune composition may contribute to a greater risk of lung cancer in females. METHODS: Data from 1056 lung cancer screenings were examined for an association between sex and lung cancer risk using time-to-event analyses. Immune profiling by flow cytometry was performed on male and female lungs of three independent mouse models: non-tumor bearing, K-ras mutated, and urethane-exposed carcinogenic. A comparable analysis was performed on human bronchoalveolar lavage samples (n = 81) from lung cancer patients. RESULTS: Of the high-risk screening cohort examined, 60 patients (5.7%) developed lung cancer during median follow-up of 43.4 months. Multivariable stepwise modeling retained female sex (hazard ratio 1.56, P < 0.01) and age (P < 0.01) as prognostic indicators for lung cancer development. Female lung immune profiles in patients included T cell phenotypes consistent with exhaustion (e.g., higher proportions of PD-1+ Ki67-; P = 0.02), an expanded pool of regulatory T cells (P = 0.03), reduced effector T cell frequencies (P = 0.008), and enhancements in suppressive myeloid populations (P = 0.02) versus males, and this is recapitulated in mouse studies. CONCLUSIONS: Female smokers display higher risk for lung cancer. In murine models and humans, female sex is associated with robust immunosuppression within the lung. Further examination of this link will be important in developing immune-based approaches to lung cancer interception and their optimal application across the sexes.

14.
Front Sociol ; 8: 1128120, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37274608

RESUMO

The intersections between aging, social minority status and housing needs in later life is a neglected area of sociological exploration, even more so for older people who identify as lesbian, gay, bisexual and trans (LGBT). Recent sociological findings indicate that older LGBT people in housing schemes stress the importance of bonding social capital and look to other people in their social networks who reflect their identities and experiences as sources of support. In this paper, we examine the insider-outsider status occupied by older LGBT residents living in housing schemes that provide some form of care and support, for example extra care and independent living schemes. We present qualitative findings generated from a mixed-methods study of social inclusion practices in housing with care in England and Wales (UK) (2019-22). In this study 15 LGBT residents participated in semi-structured interviews (55-79 years of age) across a total of 31 interviews. Through a queer gerontological lens we examine how older LGBT people are socially situated within mainstream housing schemes in which they experience partial visibility while also encountering exclusionary pressures that locate them as "the other." This insider-outsider status undermines the premise of housing with care schemes to provide safe, secure spaces to grow old. We discuss three core themes: (1) how LGBT residents navigate their outsider status in scheme life and how the intersection of disability and minority status amplifies this social location; (2) the exclusionary practices exercised by other residents that reinforce boundaries of sexual and gender normalcy; and, (3) the heightened importance of maintaining external social connections among LGBT residents. We conclude by introducing an alternative notion of marginal aging and expanding on the implications for housing providers, reflecting on their responsibilities for promoting and maintaining queer-friendly environments.

15.
J Aging Stud ; 65: 101126, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37268374

RESUMO

The COVID-19 pandemic and the lockdown measures imposed as a result affected the lives of people in all parts of society across the world. In 2020, during the first UK national lockdown, older adults (aged 70 years and over) were told to 'shield' within their homes, as they were regarded as being at higher risk of serious COVID-19 infection compared to other age groups. This paper explores older adults' experiences of COVID-19 lockdown measures whilst living in housing with care schemes for older people. The purpose is to examine the impact of the lockdown measures on scheme life including social connections amongst residents and their general everyday wellbeing during this time. We present qualitative findings based on interviews with 72 residents who took part in longitudinal and cross-sectional interviews across 26 housing with care schemes. Data were analysed using a thematic framework approach to examine specifically their experiences of living in housing with care schemes during the 2020 UK lockdown. The paper highlights that COVID-19 restrictions had a detrimental impact on the social connections and interactions of older residents living in housing with care schemes, as well as on their feelings of autonomy and independence. Despite this, residents adapted and coped with self-isolation restrictions and sought out positive ways to maintain social contact with others inside and outside to the scheme. We further highlight the tensions that providers of housing for older adults faced in promoting residents' autonomy and connectedness whilst also trying to provide a safe living environment and protect residents from risk of COVID-19 infection. Our findings apply not only to a pandemic situation but to the broader understanding of how housing with care for older adults must navigate between autonomy and support.


Assuntos
COVID-19 , Habitação , Idoso , Humanos , Controle de Doenças Transmissíveis , COVID-19/prevenção & controle , Estudos Transversais , Inglaterra , Pandemias , País de Gales
16.
ERJ Open Res ; 9(3)2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37342091

RESUMO

Background: Bronchoalveolar lavage (BAL) is an underutilised tool in the search for pulmonary disease biomarkers. While leukocytes with effector and suppressor function play important roles in airway immunity and tumours, it remains unclear if frequencies and phenotypes of BAL leukocytes can be useful parameters in lung cancer studies and clinical trials. We therefore explored the utility of BAL leukocytes as a source of biomarkers interrogating the impact of smoking, a major lung cancer risk determinant, on pulmonary immunity. Methods: In this "test case" observational study, BAL samples from 119 donors undergoing lung cancer screening and biopsy procedures were evaluated by conventional and spectral flow cytometry to exemplify the comprehensive immune analyses possible with this biospecimen. Proportions of major leukocyte populations and phenotypic markers levels were found. Multivariate linear rank sum analysis considering age, sex, cancer diagnosis and smoking status was performed. Results: Significantly increased frequencies of myeloid-derived suppressor cells and PD-L1-expressing macrophages were found in current and former smokers compared to never-smokers. While cytotoxic CD8 T-cells and conventional CD4 helper T-cell frequencies were significantly reduced in current and former smokers, expression of immune checkpoints PD-1 and LAG-3 as well as Tregs proportions were increased. Lastly, the cellularity, viability and stability of several immune readouts under cryostorage suggested BAL samples are useful for correlative end-points in clinical trials. Conclusions: Smoking is associated with heightened markers of immune dysfunction, readily assayable in BAL, that may reflect a permissive environment for cancer development and progression in the airway.

17.
Methods Mol Biol ; 2375: 13-19, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34591295

RESUMO

A major limitation in engineering vascular grafts is the lack of proper endothelium to prevent thrombosis and subsequent graft failure. Obtaining endothelial cells from patients' vasculature is intrusive and requires extensive culture time. Here we present an alternative strategy wherein abundant and easily accessible monocytes from peripheral blood are cultured and differentiated towards an endothelial-like state capable of preventing thrombosis through production of nitric oxide and formation of endothelial adherens junctions. Considering the plethora of monocytes present within peripheral blood, this method provides a robust alternative to generating endothelial cells required for vascular graft production.


Assuntos
Monócitos , Células Cultivadas , Células Endoteliais , Humanos , Óxido Nítrico , Trombose
18.
Innov Aging ; 6(7): igac061, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36451684

RESUMO

Background and Objectives: Housing with care is often lauded as a way to combat loneliness and social isolation in later life. This study examined whether housing with care created better outcomes for residents in terms of loneliness and social isolation than they might expect if they were living in the community. Research Design and Methods: A survey was distributed to residents of housing with care as part of the Diversity in Care Environments project. It was designed to enable comparison with the English Longitudinal Study of Ageing. Propensity score matching was applied to identify the effect of housing with care residence on loneliness and social isolation. Results: People living in housing with care had lower levels of loneliness than would be expected if they lived in the general community, with an average treatment effect on the treated (ATT) of -0.407 (95% CI = -0.601, -0.214). In contrast, social isolation was found to be slightly higher for residents than would be expected if they were in the community (ATT = 0.134 [95% CI = 0.022, 0.247]). Higher social isolation appears driven by less frequent contact with friends and reduced organizational membership rather than any difference in contact with family and children. Discussion and Implications: Our research has shown a positive impact on subjective social experiences from housing with care residence, despite a slight increase in objective social isolation. The findings underscore the importance of looking at loneliness and social isolation as distinct concepts as well as the effectiveness of housing with care at improving later-life outcomes.

19.
Cancer Metab ; 10(1): 17, 2022 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-36289552

RESUMO

Contrary to the "obesity paradox," which arises from retrospective studies relying on body mass index to define obesity, epidemiologic evidence suggests central or visceral obesity is associated with a higher risk for the development of lung cancer. About 60% of individuals at high risk for developing lung cancer or those already with early-stage disease are either overweight or obese. Findings from resected patient tumors and mouse lung tumor models show obesity dampens immune activity in the tumor microenvironment (TME) encouraging disease progression. In line with this, we have observed a marked, obesity-specific enhancement in the presence and phenotype of immunosuppressive regulatory T (Treg) cells in murine tumors as well as the airways of both humans and mice. Leveraging direct metabolomic measurements and robust inferred analyses from RNA-sequencing data, we here demonstrate for the first time that visceral adiposity alters the lung microenvironment via dysregulated acetyl-CoA metabolism in a direction that facilitates immune suppression and lung carcinogenesis.

20.
Adv Healthc Mater ; 11(22): e2200890, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36112115

RESUMO

A strategy to recruit monocytes (MCs) from blood to regenerate vascular tissue from unseeded (cell-free) tissue engineered vascular grafts is presented. When immobilized on the surface of vascular grafts, the fusion protein, H2R5 can capture blood-derived MC under static or flow conditions in a shear stress dependent manner. The bound MC turns into macrophages (Mϕ) expressing both M1 and M2 phenotype specific genes. When H2R5 functionalized acellular-tissue engineered vessels (A-TEVs) are implanted into the mouse aorta, they remain patent and form a continuous endothelium expressing both endothelial cell (EC) and MC specific proteins. Underneath the EC layer, multiple cells layers are formed coexpressing both smooth muscle cell (SMC) and MC specific markers. Lineage tracing analysis using a novel CX3CR1-confetti mouse model demonstrates that fluorescently labeled MC populates the graft lumen by two and four weeks postimplantation, providing direct evidence in support of MC/Mϕ recruitment to the graft lumen. Given their abundance in the blood, circulating MCs may be a great source of cells that contribute directly to the endothelialization and vascular wall formation of acellular vascular grafts under the right chemical and biomechanical cues.


Assuntos
Monócitos , Engenharia Tecidual , Camundongos , Animais , Monócitos/metabolismo , Miócitos de Músculo Liso , Células Endoteliais , Prótese Vascular , Endotélio Vascular
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