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1.
Virol J ; 20(1): 164, 2023 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-37488599

RESUMO

BACKGROUND: Porcine epidemic diarrhea virus (PEDV) is an α-coronavirus that causes highly contagious intestinal infectious disease, involving clinically characterized by diarrhea, dehydration, vomiting, and high mortality to suckling piglets. As a strategy for antiviral therapy, artificial microRNA (amiRNA) mediated suppression of viral replication has recently become increasingly important. In this study, we evaluated the advantages of using an amiRNA vector against PEDV. METHODS: In this study, we evaluated the advantages of using an amiRNA vector against PEDV. We designed two single amiRNA sequences for different conserved sequences of the PEDV S and N genes, and tested their inhibitory effects on PEDV in Vero cells. RESULTS: It was obvious from the CCK-8 results that the transient transfection of amiRNA was non-toxic to the cells. In addition, our results showed that the transient expression of two amiRNAs (amiRNA-349 and amiRNA-1447) significantly reduced the expression of viral RNA and protein in the cells. The TCID50 results showed that the release of virus particles into the culture supernatant was significantly reduced, with an effect as high as 90%. To avoid virus mutation escape, the above two single amiRNA sequences were tandem in this study (amiRNA-349 + 1447), enabling a single microRNA to be expressed simultaneously. The real-time PCR and Western blot results showed that the inhibitory effect was significantly enhanced in each of the different time periods. The TCID50 results showed that the release of virus particles in the culture supernatant was significantly reduced at the different time periods. CONCLUSIONS: In summary, these results suggest that an RNAi based on amiRNA targeting the conserved region of the virus is an effective method to improve PEDV nucleic acid inhibitors and provide a novel treatment strategy for PEDV infection.


Assuntos
Coronavirus , MicroRNAs , Vírus da Diarreia Epidêmica Suína , Animais , Suínos , Chlorocebus aethiops , Células Vero , Interferência de RNA
2.
Ethn Health ; 28(6): 836-852, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36907661

RESUMO

OBJECTIVE: To determine whether inequities in COVID-19 infection and hospitalization differ from those for common medical conditions: influenza, appendicitis, and all-cause hospitalization. DESIGN: Retrospective study based on electronic health records of three healthcare systems in San Francisco (university, public, and community) examining (1) racial/ethnic distribution in cases and hospitalization among patients with diagnosed COVID-19 (March-August 2020) and patients with diagnosed influenza, diagnosed appendicitis, or all-cause hospitalization (August 2017-March 2020), and (2) sociodemographic predictors of hospitalization among those with diagnosed COVID-19 and influenza. RESULTS: Patients 18 years or older with diagnosed COVID-19 (N = 3934), diagnosed influenza (N = 5932), diagnosed appendicitis (N = 1235), or all-cause hospitalization (N = 62,707) were included in the study. The age-adjusted racial/ethnic distribution of patients with diagnosed COVID-19 differed from that of patients with diagnosed influenza or appendicitis for all healthcare systems, as did hospitalization from these conditions compared to any cause. For example, in the public healthcare system, 68% of patients with diagnosed COVID-19 were Latine, compared with 43% of patients with diagnosed influenza, and 48% of patients with diagnosed appendicitis (p < 0.05). In multivariable logistic regressions, COVID-19 hospitalizations were associated with male sex, Asian and Pacific Islander race/ethnicity, Spanish language, and public insurance in the university healthcare system, and Latine race/ethnicity and obesity in the community healthcare system. Influenza hospitalizations were associated with Asian and Pacific Islander and other race/ethnicity in the university healthcare system, obesity in the community healthcare system, and Chinese language and public insurance in both the university and community healthcare systems. CONCLUSIONS: Racial/ethnic and sociodemographic inequities in diagnosed COVID-19 and hospitalization differed from those for diagnosed influenza and other medical conditions, with consistently higher odds among Latine and Spanish-speaking patients. This work highlights the need for disease-specific public health efforts in at-risk communities in addition to structural upstream interventions.


Assuntos
Apendicite , COVID-19 , Influenza Humana , Humanos , Masculino , Apendicite/epidemiologia , Negro ou Afro-Americano/estatística & dados numéricos , Estudos de Coortes , COVID-19/epidemiologia , Hospitalização/estatística & dados numéricos , Influenza Humana/epidemiologia , Obesidade/epidemiologia , Estudos Retrospectivos , População Branca/estatística & dados numéricos , São Francisco/epidemiologia , Feminino , Adolescente , Adulto Jovem , Adulto , Nativo Asiático-Americano do Havaí e das Ilhas do Pacífico/estatística & dados numéricos , Hispânico ou Latino/estatística & dados numéricos
3.
Am J Epidemiol ; 190(11): 2300-2313, 2021 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-34215866

RESUMO

To measure disparities in coronavirus disease 2019 (COVID-19) hospitalization and intensive care unit (ICU) transfer among racially/ethnically marginalized groups before and after implementation of the California statewide shelter-in-place (SIP) policy, we conducted a retrospective cohort study within a health-care system in California. COVID-19 patients diagnosed from January 1, 2020, to August 31, 2020, were identified from electronic health records. We examined hospitalizations and ICU transfers by race/ethnicity and pandemic period using logistic regression. Among 16,520 people with COVID-19 (mean age = 46.6 (standard deviation, 18.4) years; 54.2% women), during the post-SIP period, patients were on average younger and a larger proportion were Hispanic. In adjusted models, odds of hospitalization were 20% lower post-SIP as compared with the SIP period, yet all non-White groups had higher odds (odds ratios = 1.6-2.1) than non-Hispanic White individuals, regardless of period. Among hospitalized patients, odds of ICU transfer were 33% lower post-SIP than during SIP. Hispanic and Asian patients had higher odds than non-Hispanics. Disparities in hospitalization persisted and ICU risk became more pronounced for Asian and Hispanic patients post-SIP. Policy-makers should consider ways to proactively address racial/ethnic inequities in risk when considering future population-level policy interventions for public health crises.


Assuntos
COVID-19/etnologia , Disparidades nos Níveis de Saúde , Hospitalização/estatística & dados numéricos , Unidades de Terapia Intensiva/estatística & dados numéricos , Grupos Raciais/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/epidemiologia , COVID-19/terapia , COVID-19/virologia , California/epidemiologia , Comorbidade , Feminino , Política de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , SARS-CoV-2 , Adulto Jovem
4.
BMC Fam Pract ; 22(1): 256, 2021 12 24.
Artigo em Inglês | MEDLINE | ID: mdl-34952582

RESUMO

BACKGROUND: There is increased recognition in clinical settings of the importance of documenting, understanding, and addressing patients' social determinants of health (SDOH) to improve health and address health inequities. This study evaluated a pilot of a standardized SDOH screening questionnaire and workflow in an ambulatory clinic within a large integrated health network in Northern California. METHODS: The pilot screened for SDOH needs using an 11-question Epic-compatible paper questionnaire assessing eight SDOH and health behavior domains: financial resource, transportation, stress, depression, intimate partner violence, social connections, physical activity, and alcohol consumption. Eligible patients for the pilot receiving a Medicare wellness, adult annual, or new patient visits during a five-week period (February-March, 2020), and a comparison group from the same time period in 2019 were identified. Sociodemographic data (age, sex, race/ethnicity, and payment type), visit type, length of visit, and responses to SDOH questions were extracted from electronic health records, and a staff experience survey was administered. The evaluation was guided by the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework. RESULTS: Two-hundred eighty-nine patients were eligible for SDOH screening. Responsiveness by domain ranged from 55 to 67%, except for depression. Half of patients had at least one identified social need, the most common being stress (33%), physical activity (22%), alcohol (12%), and social connections (6%). Physical activity needs were identified more in females (81% vs. 19% in males, p < .01) and at new patient/transfer visits (48% vs. 13% at Medicare wellness and 38% at adult wellness visits, p < .05). Average length of visit was 39.8 min, which was 1.7 min longer than that in 2019. Visit lengths were longer among patients 65+ (43.4 min) and patients having public insurance (43.6 min). Most staff agreed that collecting SDOH data was relevant and accepted the SDOH questionnaire and workflow but highlighted opportunities for improvement in training and connecting patients to resources. CONCLUSION: Use of evidence-based SDOH screening questions and associated workflow was effective in gathering patient SDOH information and identifying social needs in an ambulatory setting. Future studies should use qualitative data to understand patient and staff experiences with collecting SDOH information in healthcare settings.


Assuntos
Desigualdades de Saúde , Determinantes Sociais da Saúde , Idoso , Feminino , Humanos , Masculino , Medicare , Encaminhamento e Consulta , Inquéritos e Questionários , Estados Unidos , Fluxo de Trabalho
5.
Ann Emerg Med ; 74(5): 622-631, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31272820

RESUMO

STUDY OBJECTIVE: We examine racial and ethnic differences in opioid prescribing and dosing for long bone fractures at emergency department (ED) discharge. METHODS: We conducted an electronic health records-based cross-sectional study of adults with long bone fractures who presented to the ED across 22 sites from a health care delivery system (2016 to 2017). We examined differences in opioid prescribing at ED discharge and, among patients with a prescription, differences in opioid dosing (measured as morphine milligram equivalents) by race/ethnicity, using regression modeling with statistical adjustment for patient, fracture, and prescriber characteristics. RESULTS: A total of 11,576 patients with long bone fractures were included in the study; 64.4% were non-Hispanic white; 16.4%, 7.3%, 5.8%, and 5.1%, respectively, were Hispanic, Asian, black, and of other or unknown race; and 65.6% received an opioid at discharge. After adjusting for other factors, rates of opioid prescribing were not different by race/ethnicity; however, among patients with an opioid prescription, total morphine milligram equivalent units prescribed were 4.3%, 6.0%, and 8.1% less for Hispanics, blacks, and Asians relative to non-Hispanic whites. CONCLUSION: Racial and ethnic minority groups with long bone fractures receive similar frequencies of opioid prescriptions at discharge, with a small potency difference. How this affects pain relief and why it happens is unclear.


Assuntos
Analgésicos Opioides/uso terapêutico , Fraturas Ósseas/complicações , Disparidades nos Níveis de Saúde , Dor Pós-Operatória/tratamento farmacológico , Alta do Paciente , Padrões de Prática Médica/estatística & dados numéricos , Adulto , California/epidemiologia , Estudos Transversais , Serviço Hospitalar de Emergência , Etnicidade , Feminino , Fraturas Ósseas/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Grupos Minoritários , Dor Pós-Operatória/epidemiologia , Adulto Jovem
6.
Front Psychol ; 15: 1295709, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38860036

RESUMO

Introduction: This study investigates the influence of gamification integration on language learning achievement among Chinese students while probing the mediating role of learners' motivation. Furthermore, it extends the boundaries of this investigation by exploring the moderating effect of digital literacy as a psychological predisposition. Methods: Data is collected through surveys from Chinese students enrolled in linguistic programs, employing a stratified random sampling technique and analyzed via SmartPLS SEM. Results: The findings affirm the significant and positive impact of gamification integration on language learning achievement. The study introduces a moderated mediation model where learners' motivation serves as the mediator, and digital literacy acts as a moderator, further accentuating the significant impact of this integrated approach. Discussion: This research advances our theoretical understanding of language learning, validating gamification's effectiveness as a motivational tool, and introduces digital literacy as a critical factor, providing deeper insights into personalized language learning experiences.

7.
Acad Emerg Med ; 30(8): 809-818, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36876410

RESUMO

OBJECTIVES: Racial and ethnic minorities receive opioid prescriptions at lower rates and dosages than White patients. Though opioid stewardship interventions can improve or exacerbate these disparities, there is little evidence about these effects. We conducted a secondary analysis of a cluster-randomized controlled trial conducted among 438 clinicians from 21 emergency departments and 27 urgent care clinics. Our objective was to determine whether randomly allocated opioid stewardship clinician feedback interventions that were designed to reduce opioid prescriptions had unintended effects on disparities in prescribing by patient race and ethnicity. METHODS: The primary outcome was likelihood of receiving a low-pill prescription (low ≤10 pills, medium 11-19 pills, high ≥20 pills). Generalized mixed-effects models were used to determine patient characteristics associated with low-pill prescriptions during the baseline period. These models were then used to determine whether receipt of a low-pill prescription varied by patient race or ethnicity during the intervention period between usual care and three opioid stewardship interventions: (1) individual audit feedback, (2) peer comparison feedback, and (3) combined (individual audit + peer comparison) feedback. RESULTS: Compared with White patients, Black patients were more likely to receive a low-pill prescription during the baseline (adjusted odds ratio [OR] 1.18, 95% confidence interval [CI] 1.06-1.31, p = 0.002) and intervention (adjusted OR 1.43, 95% CI 1.07-1.91, p = 0.015). While combined feedback was associated with an overall increase in low-pill prescriptions as intended (adjusted OR 1.89, 95% CI 1.28-2.78, p = 0.001), there were no significant differences in treatment effects of any of the interventions by patient race and ethnicity. CONCLUSIONS: Combined individual audit and peer comparison feedback was associated with fewer opioid pills per prescription equally by patient race and ethnicity. However, the intervention did not significantly close the baseline disparity in prescribing by race.


Assuntos
Analgésicos Opioides , Padrões de Prática Médica , Humanos , Analgésicos Opioides/uso terapêutico , Retroalimentação , Serviço Hospitalar de Emergência , Assistência Ambulatorial
8.
Am J Med Qual ; 38(3): 129-136, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37017283

RESUMO

Peer comparison feedback is a promising strategy for reducing opioid prescribing and opioid-related harms. Such comparisons may be particularly impactful among underestimating clinicians who do not perceive themselves as high prescribers relative to their peers. But peer comparisons could also unintentionally increase prescribing among overestimating clinicians who do not perceive themselves as lower prescribers than peers. The objective of this study was to assess if the impact of peer comparisons varied by clinicians' preexisting opioid prescribing self-perceptions. Subgroup analysis of a randomized trial of peer comparison interventions among emergency department and urgent care clinicians was used. Generalized mixed-effects models were used to assess whether the impact of peer comparisons, alone or combined with individual feedback, varied by underestimating or overestimating prescriber status. Underestimating and overestimating prescribers were defined as those who self-reported relative prescribing amounts that were lower and higher, respectively, than actual relative baseline amounts. The primary outcome was pills per opioid prescription. Among 438 clinicians, 54% (n = 236) provided baseline prescribing self-perceptions and were included in this analysis. Overall, 17% (n = 40) were underestimating prescribers whereas 5% (n = 11) were overestimating prescribers. Underestimating prescribers exhibited a differentially greater decrease in pills per prescription compared to nonunderestimating clinicians when receiving peer comparison feedback (1.7 pills, 95% CI, -3.2 to -0.2 pills) or combined peer and individual feedback (2.8 pills, 95% CI, -4.8 to -0.8 pills). In contrast, there were no differential changes in pills per prescription for overestimating versus nonoverestimating prescribers after receiving peer comparison (1.5 pills, 95% CI, -0.9 to 3.9 pills) or combined peer and individual feedback (3.0 pills, 95% CI, -0.3 to 6.2 pills). Peer comparisons were more impactful among clinicians who underestimated their prescribing compared to peers. By correcting inaccurate self-perceptions, peer comparison feedback can be an effective strategy for influencing opioid prescribing.


Assuntos
Analgésicos Opioides , Médicos , Humanos , Analgésicos Opioides/uso terapêutico , Retroalimentação , Padrões de Prática Médica , Serviço Hospitalar de Emergência
9.
Drug Deliv ; 29(1): 238-253, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35001784

RESUMO

Photodynamic therapy (PDT) has been applied in cancer treatment by utilizing reactive oxygen species (ROS) to kill cancer cells. However, the effectiveness of PDT is greatly reduced due to local hypoxia. Hypoxic activated chemotherapy combined with PDT is expected to be a novel strategy to enhance anti-cancer therapy. Herein, a novel liposome (LCT) incorporated with photosensitizer (PS) and bioreductive prodrugs was developed for PDT-activated chemotherapy. In the design, CyI, an iodinated cyanine dye, which could simultaneously generate enhanced ROS and heat than other commonly used cyanine dyes, was loaded into the lipid bilayer; while tirapazamine (TPZ), a hypoxia-activated prodrug was encapsulated in the hydrophilic nucleus. Upon appropriate near-infrared (NIR) irradiation, CyI could simultaneously produce ROS and heat for synergistic PDT and photothermal therapy (PTT), as well as provide fluorescence signals for precise real-time imaging. Meanwhile, the continuous consumption of oxygen would result in a hypoxia microenvironment, further activating TPZ free radicals for chemotherapy, which could induce DNA double-strand breakage and chromosome aberration. Moreover, the prepared LCT could stimulate acute immune response through PDT activation, leading to synergistic PDT/PTT/chemo/immunotherapy to kill cancer cells and reduce tumor metastasis. Both in vitro and in vivo results demonstrated improved anticancer efficacy of LCT compared with traditional PDT or chemotherapy. It is expected that these iodinated cyanine dyes-based liposomes will provide a powerful and versatile theranostic strategy for tumor target phototherapy and PDT-induced chemotherapy.


Assuntos
Antineoplásicos/farmacologia , Hipóxia/patologia , Sistemas de Liberação de Fármacos por Nanopartículas/química , Fármacos Fotossensibilizantes/farmacologia , Fototerapia/métodos , Tirapazamina/farmacologia , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacocinética , Sobrevivência Celular/efeitos dos fármacos , Química Farmacêutica , Aberrações Cromossômicas/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Lipossomos/química , Camundongos , Camundongos Endogâmicos BALB C , Tamanho da Partícula , Fármacos Fotossensibilizantes/administração & dosagem , Fármacos Fotossensibilizantes/farmacocinética , Espécies Reativas de Oxigênio/metabolismo , Propriedades de Superfície , Tirapazamina/administração & dosagem , Tirapazamina/farmacocinética , Ensaios Antitumorais Modelo de Xenoenxerto
10.
Health Aff (Millwood) ; 41(3): 424-433, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35254932

RESUMO

An initial opioid prescription with a greater number of pills is associated with a greater risk for future long-term opioid use, yet few interventions have reliably influenced individual clinicians' prescribing. Our objective was to evaluate the effect of feedback interventions for clinicians in reducing opioid prescribing. The interventions included feedback on a clinician's outlier prescribing (individual audit feedback), peer comparison, and both interventions combined. We conducted a four-arm factorial pragmatic cluster randomized trial at forty-eight emergency department (ED) and urgent care (UC) sites in the western US, including 263 ED and 175 UC clinicians with 294,962 patient encounters. Relative to usual care, there was a significant decrease in pills per prescription both for peer comparison feedback (-0.8) and for the combination of peer comparison and individual audit feedback (-1.2). This decrease was sustained during follow-up. There were no significant changes for individual audit feedback alone, and no interventions changed the proportion of encounters with an opioid prescription.


Assuntos
Analgésicos Opioides , Padrões de Prática Médica , Analgésicos Opioides/uso terapêutico , Serviço Hospitalar de Emergência , Retroalimentação , Humanos , Prescrição Inadequada , Grupo Associado
11.
Health Equity ; 5(1): 476-483, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34316531

RESUMO

Purpose: The coronavirus pandemic has created the greatest public health crisis in a century, causing >500,000 deaths in the United States alone. Minoritized and socioeconomically disadvantaged groups have borne a disproportionate burden of severe illness, hospitalization, and death from COVID-19. Recently developed FDA-approved vaccines have been shown to significantly reduce severe COVID-19-related outcomes. Vaccination campaigns have the potential to advance health equity by prioritizing allocation to those at highest risk while striving for herd immunity. Large integrated health systems have been faced with the daunting task of meeting the rapidly evolving needs of diverse patient populations for the provision of population-based testing, treatment, education, and now vaccine distribution. We have designed a COVID-19 vaccine equity index (CVEI) to guide health system vaccination strategy. Methods: We considered proportion unvaccinated within a health care system. We then used real-time readily available electronic health record (EHR) COVID-19 testing positivity and proportion hospitalized to measure burden of illness by race/ethnicity. We used conditional probability and statistical theory to measure equity for unvaccinated individuals and to derive an index to highlight these inequities for specific subgroups. Results: We present an illustrative hypothetical example using simulated data for which we calculated the CVEI for non-Hispanic White, non-Hispanic Black, non-Hispanic Asian, and Hispanic patients. In the example, non-Hispanic Black and Hispanic patients had inequitable outcomes. Conclusion: The index can be widely implemented to promote more equitable outcomes among racial/ethnic groups, reducing morbidity and mortality within the overall population as we pursue the collective goal of herd immunity through mass vaccination.

12.
Popul Health Manag ; 23(6): 430-437, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-31816257

RESUMO

Frequent emergency department (ED) utilization is an indicator of unmet health and social needs, especially among patients with mental and physical health problems. The authors aimed to characterize frequent ED utilizers and drivers of multiple ED use, including presence of serious mental illness (SMI), across 2 large health care systems in Northern California. Using electronic health records and a data-sharing platform, a cross-sectional analysis was conducted of patients aged 18+ years with ≥10 ED visits in 2016. Logistic regression was used to determine factors associated with multiple ED use versus single ED use. Among the 8036 patients who met inclusion criteria, the mean age was 55.9 years (95% CI = 55.5-56.4), 53% were female, 54% were non-Hispanic white, and 38% had any SMI. Overall, 51% of patients were single ED utilizers. Patients ages ≥65 years were less likely to use multiple EDs compared to younger patients (ages 18-23) (OR = 0.3, 95% CI = 0.2-0.4). African Americans exhibited more than 3 times the likelihood of multi-ED use compared to non-Hispanic whites (OR = 3.8, 95% CI = 3.3-4.3). A diagnosis of any SMI (OR = 2.3 [95% CI: 2.1-2.6]), major depressive disorder (OR = 1.3, 95% CI = 1.1-1.4), schizophrenia (OR = 2.1, 95% CI = 1.6-2.6), or suicidal attempts/ideation (OR = 2.7, 95% CI = 2.1-3.6) was significantly associated with increased likelihood of multi-ED use. Findings indicate heterogeneity in regional utilization patterns among frequent ED utilizers, with mental illness increasing the likelihood of multi-ED use.


Assuntos
Transtorno Depressivo Maior , Transtornos Mentais , Adolescente , Adulto , Idoso , Estudos Transversais , Serviço Hospitalar de Emergência , Feminino , Humanos , Modelos Logísticos , Transtornos Mentais/epidemiologia , Transtornos Mentais/terapia , Pessoa de Meia-Idade , Adulto Jovem
13.
Theranostics ; 10(20): 9132-9152, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32802183

RESUMO

Photodynamic therapy (PDT) is a promising strategy in cancer treatment that utilizes photosensitizers (PSs) to produce reactive oxygen species (ROS) and eliminate cancer cells under specific wavelength light irradiation. However, special tumor environments, such as those with overexpression of glutathione (GSH), which will consume PDT-mediated ROS, as well as hypoxia in the tumor microenvironment (TME) could lead to ineffective treatment. Moreover, PDT is highly light-dependent and therefore can be hindered in deep tumor cells where light cannot easily penetrate. To solve these problems, we designed oxygen-dual-generating nanosystems MnO2@Chitosan-CyI (MCC) for enhanced phototherapy. Methods: The TME-sensitive nanosystems MCC were easily prepared through the self-assembly of iodinated indocyanine green (ICG) derivative CyI and chitosan, after which the MnO2 nanoparticles were formed as a shell by electrostatic interaction and Mn-N coordinate bonding. Results: When subjected to NIR irradiation, MCC offered enhanced ROS production and heat generation. Furthermore, once endocytosed, MnO2 could not only decrease the level of GSH but also serve as a highly efficient in situ oxygen generator. Meanwhile, heat generation-induced temperature increase accelerated in vivo blood flow, which effectively relieved the environmental tumor hypoxia. Furthermore, enhanced PDT triggered an acute immune response, leading to NIR-guided, synergistic PDT/photothermal/immunotherapy capable of eliminating tumors and reducing tumor metastasis. Conclusion: The proposed novel nanosystems represent an important advance in altering TME for improved clinical PDT efficacy, as well as their potential as effective theranostic agents in cancer treatment.


Assuntos
Fatores Imunológicos/metabolismo , Nanopartículas/uso terapêutico , Hipóxia Tumoral/efeitos dos fármacos , Hipóxia Tumoral/fisiologia , Microambiente Tumoral/fisiologia , Animais , Linhagem Celular , Linhagem Celular Tumoral , Feminino , Glutationa/metabolismo , Humanos , Verde de Indocianina/metabolismo , Masculino , Compostos de Manganês/uso terapêutico , Camundongos , Camundongos Endogâmicos BALB C , Óxidos/uso terapêutico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Fototerapia/métodos , Células RAW 264.7 , Espécies Reativas de Oxigênio/metabolismo , Nanomedicina Teranóstica/métodos
14.
Nanoscale ; 12(20): 11008-11025, 2020 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-32301458

RESUMO

Photodynamic therapy (PDT), as one of the most powerful photo-therapeutic strategies for cancer treatment with minimum invasiveness, can effectively damage local tumor cells and significantly induce systemic antitumor immunity. However, current nanotechnology-assisted PDT-immunomodulators have either poor penetration for deep tumors or low singlet oxygen generation. Herein, we construct a novel theranostic nanocarrier (HA-PEG-CyI, HPC) by inducing the self-assembly of PEGylated CyI and attaching the ligand HA to its surface. The prepared HPC can be used as an ideal PDT-immunomodulator for synergistic cancer therapy. CyI is an iodinated-cyanine dye with enhanced singlet oxygen generation ability as well as excellent photo-to-photothermal and near-infrared fluorescence imaging properties. Under 808 nm laser irradiation, the prepared HPC can generate both reactive oxygen species (ROS) and elevate temperature which can subsequently result in apoptosis and necrosis at tumor sites. Moreover, the HPC-induced cell death can generate a series of acute inflammatory reactions, leading to systemic immunity induction and secondary death of tumor cells, which further results in reducing tumor recurrence. In vitro and in vivo results show that HPC can enhance the tumor targeting efficacy, generate ROS efficiently and exhibit a high temperature response under NIR irradiation, which working together can activate immune responses for synergistic phototherapy on tumor cells. Accordingly, the proposed multi-functional HPC nanocarriers represent an important advance in PDT and can be used as a superior cancer treatment strategy with great promise for clinical applications.


Assuntos
Carbocianinas , Portadores de Fármacos , Hidrocarbonetos Iodados , Fatores Imunológicos , Nanoestruturas , Neoplasias Experimentais , Fotoquimioterapia , Animais , Apoptose/efeitos dos fármacos , Carbocianinas/química , Carbocianinas/farmacocinética , Carbocianinas/farmacologia , Linhagem Celular Tumoral , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Feminino , Humanos , Hidrocarbonetos Iodados/química , Hidrocarbonetos Iodados/farmacocinética , Hidrocarbonetos Iodados/farmacologia , Fatores Imunológicos/química , Fatores Imunológicos/farmacocinética , Fatores Imunológicos/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Nanoestruturas/química , Nanoestruturas/uso terapêutico , Neoplasias Experimentais/diagnóstico por imagem , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/metabolismo , Células RAW 264.7
15.
Health Aff (Millwood) ; 39(7): 1253-1262, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32437224

RESUMO

As the novel coronavirus disease (COVID-19) pandemic spreads throughout the United States, evidence is mounting that racial and ethnic minorities and socioeconomically disadvantaged groups are bearing a disproportionate burden of illness and death. We conducted a retrospective cohort analysis of COVID-19 patients at Sutter Health, a large integrated health system in northern California, to measure potential disparities. We used Sutter's integrated electronic health record to identify adults with suspected and confirmed COVID-19, and we used multivariable logistic regression to assess risk of hospitalization, adjusting for known risk factors, such as race/ethnicity, sex, age, health, and socioeconomic variables. We analyzed 1,052 confirmed cases of COVID-19 from the period January 1-April 8, 2020. Among our findings, we observed that compared with non-Hispanic white patients, non-Hispanic African American patients had 2.7 times the odds of hospitalization, after adjustment for age, sex, comorbidities, and income. We explore possible explanations for this, including societal factors that either result in barriers to timely access to care or create circumstances in which patients view delaying care as the most sensible option. Our study provides real-world evidence of racial and ethnic disparities in the presentation of COVID-19.


Assuntos
Infecções por Coronavirus/epidemiologia , Disparidades em Assistência à Saúde/economia , Disparidades em Assistência à Saúde/etnologia , Cobertura do Seguro/estatística & dados numéricos , Pandemias/estatística & dados numéricos , Pneumonia Viral/epidemiologia , Pobreza/estatística & dados numéricos , Adulto , Fatores Etários , Idoso , COVID-19 , California/epidemiologia , Estudos de Coortes , Infecções por Coronavirus/prevenção & controle , Bases de Dados Factuais , Etnicidade/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Grupos Minoritários/estatística & dados numéricos , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Prevalência , Estudos Retrospectivos , Medição de Risco , Fatores Sexuais , Fatores Socioeconômicos , Análise de Sobrevida
16.
Environ Sci Pollut Res Int ; 26(7): 7102-7114, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30645744

RESUMO

Mg-Al, Zn-Al and Mg-Fe magnetic layered double hydroxide (LDH) adsorbents were synthesized. The adsorption effect and influencing factors of these adsorbents were explored, and the adsorption mechanism of phosphorus was studied with advanced instruments. The results showed that the best adsorption performance was observed when the molar ratio of metals was 3 for the magnetic LDH adsorbents, and the maximum adsorption amount for phosphorus was 74.8, 80.8 and 67.8 mg/g for Mg-Al, Zn-Al and Mg-Fe LDHs, respectively. Pseudo-second-order kinetics could be used to describe the adsorption process of phosphorus onto the magnetic LDHs. The adsorption of phosphorus onto the magnetic LDHs was an exothermic process. Lower temperatures were favourable for adsorption, and the adsorption of phosphorus onto the magnetic LDHs was a spontaneous process. When the solid-liquid ratios were 0.10 g/L, 0.10 g/L and 0.05 g/L for Mg-Al, Zn-Al and Mg-Fe magnetic LDHs, respectively, the highest adsorption amount of phosphorus was achieved for each magnetic LDH. The maximum adsorption amount was observed at pH values of 6.0-8.0. The inhibitory effect of HCO3- on the adsorption capacity of phosphorus onto the magnetic LDHs was the strongest at a higher HCO3- concentration level. The relative content of -OH significantly reduced after adsorption of phosphorus by the FTIR analysis, which indicated that the mechanism of phosphorus removal was mainly through the exchange between hydroxyl on the adsorbent surface and phosphorus in water. XPS studies showed that oxygen provided electrons during the adsorption of phosphorus.


Assuntos
Fósforo/química , Poluentes Químicos da Água/química , Purificação da Água/métodos , Adsorção , Complexos de Coordenação/química , Hidróxidos/química , Cinética , Água , Zinco
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