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1.
JMIR Form Res ; 7: e39765, 2023 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-36525333

RESUMEN

BACKGROUND: Contact tracing is a vital public health tool used to prevent the spread of infectious diseases. However, traditional interview-format contact tracing (TCT) is labor-intensive and time-consuming and may be unsustainable for large-scale pandemics such as COVID-19. OBJECTIVE: In this study, we aimed to address the limitations of TCT. The Yale School of Engineering developed a Hardware-Assisted Bluetooth-based Infection Tracking (HABIT) device. Following the successful implementation of HABIT in a university setting, this study sought to evaluate the performance and implementation of HABIT in a high school setting using an embedded mixed methods design. METHODS: In this pilot implementation study, we first assessed the performance of HABIT using mock case simulations in which we compared contact tracing data collected from mock case interviews (TCT) versus Bluetooth devices (HABIT). For each method, we compared the number of close contacts identified and identification of unique contacts. We then conducted an embedded mixed methods evaluation of the implementation outcomes of HABIT devices using pre- and postimplementation quantitative surveys and qualitative focus group discussions with users and implementers according to the Reach, Effectiveness, Adoption, Implementation, and Maintenance framework. RESULTS: In total, 17 students and staff completed mock case simulations in which 161 close contact interactions were detected by interview or Bluetooth devices. We detected significant differences in the number of close contacts detected by interview versus Bluetooth devices (P<.001), with most (127/161, 78.9%) contacts being reported by interview only. However, a significant number (26/161, 16.1%; P<.001) of contacts were uniquely identified by Bluetooth devices. The interface, ease of use, coherence, and appropriateness were highly rated by both faculty and students. HABIT provided emotional security to users. However, the prototype design and technical difficulties presented barriers to the uptake and sustained use of HABIT. CONCLUSIONS: Implementation of HABIT in a high school was impeded by technical difficulties leading to decreased engagement and adherence. Nonetheless, HABIT identified a significant number of unique contacts not reported by interview, indicating that electronic technologies may augment traditional contact tracing once user preferences are accommodated and technical glitches are overcome. Participants indicated a high degree of acceptance, citing emotional reassurance and a sense of security with the device.

2.
J Public Health Manag Pract ; 28(6): 728-738, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36194817

RESUMEN

CONTEXT: The COVID-19 pandemic has disproportionately impacted vulnerable populations, including those who are non-English-speaking and those with lower socioeconomic status; yet, participation of these groups in contact tracing was initially low. Distrust of government agencies, anticipated COVID-19-related stigma, and language and cultural barriers between contact tracers and communities are common challenges. PROGRAM: The Community Outreach Specialist (COS) program was established within the Connecticut Department of Public Health (DPH) COVID-19 contact tracing program to encourage participation in contact tracing and address a need for culturally competent care and social and material support among socially vulnerable and non-English-speaking populations in 11 high-burden jurisdictions in Connecticut. IMPLEMENTATION: In partnership with state and local health departments, we recruited 25 COS workers with relevant language skills from target communities and trained them to deliver contact tracing services to vulnerable and non-English speaking populations. EVALUATION: We conducted a cross-sectional analysis using data from ContaCT, DPH's enterprise contact tracing system. Overall, the COS program enrolled 1938 cases and 492 contacts. The proportion of residents reached (ie, called and interviewed) in the COS program was higher than that in the regular contact tracing program for both cases (70% vs 57%, P < .001) and contacts (84% vs 64%, P < .001). After adjusting for client age, sex, race and ethnicity, language, and jurisdiction, we found that the COS program was associated with increased reach for contacts (odds ratio [OR] = 1.52; 95% confidence interval [95% CI], 1.17-1.99) but not for cases (OR = 0.78; 95% CI, 0.70-0.88). Rapid qualitative analysis of programmatic field notes and meeting reports provided evidence that the COS program was feasible and acceptable to clients and contributed to COVID-19 education and communication efforts. CONCLUSION: A COS program employing a client-centered, community-engaged strategy for reaching vulnerable and non-English-speaking populations was feasible and more effective at reaching contacts than standard COVID-19 contact tracing.


Asunto(s)
COVID-19 , Equidad en Salud , COVID-19/epidemiología , COVID-19/prevención & control , Relaciones Comunidad-Institución , Connecticut/epidemiología , Trazado de Contacto , Estudios Transversales , Humanos , Pandemias/prevención & control
3.
BMC Public Health ; 22(1): 1963, 2022 10 25.
Artículo en Inglés | MEDLINE | ID: mdl-36284292

RESUMEN

BACKGROUND: Low engagement in contact tracing for COVID-19 dramatically reduces its impact, but little is known about how experiences, environments and characteristics of cases and contacts influence engagement. METHODS: We recruited a convenience sample of COVID-19 cases and contacts from the New Haven Health Department's contact tracing program for interviews about their contact tracing experiences. We analyzed transcripts thematically, organized themes using the Capability, Opportunity, Motivation, Behavior (COM-B) model, and identified candidate interventions using the linked Behavior Change Wheel Framework. RESULTS: We interviewed 21 cases and 12 contacts. Many felt physically or psychologically incapable of contact tracing participation due to symptoms or uncertainty about protocols. Environmental factors and social contacts also influenced engagement. Finally, physical symptoms, emotions and low trust in and expectations of public health authorities influenced motivation to participate. CONCLUSION: To improve contact tracing uptake, programs should respond to clients' physical and emotional needs; increase clarity of public communications; address structural and social factors that shape behaviors and opportunities; and establish and maintain trust. We identify multiple potential interventions that may help achieve these goals.


Asunto(s)
COVID-19 , Trazado de Contacto , Humanos , Trazado de Contacto/métodos , Investigación Cualitativa , Salud Pública , Motivación
4.
BMJ Open ; 12(5): e061508, 2022 05 25.
Artículo en Inglés | MEDLINE | ID: mdl-35613785

RESUMEN

INTRODUCTION: HIV status awareness is important for household contacts of patients with tuberculosis (TB). Home HIV testing during TB contact investigation increases HIV status awareness. Social interactions during home visits may influence perceived stigma and uptake of HIV testing. We designed an intervention to normalise and facilitate uptake of home HIV testing with five components: guided selection of first tester; prosocial invitation scripts; opt-out framing; optional sharing of decisions to test; and masking of decisions not to test. METHODS AND ANALYSIS: We will evaluate the intervention effect in a household-randomised controlled trial. The primary aim is to assess whether contacts offered HIV testing using the norming strategy will accept HIV testing more often than those offered testing using standard strategies. Approximately 198 households will be enrolled through three public health facilities in Kampala, Uganda. Households will be randomised to receive the norming or standard strategy and visited by a community health worker (CHW) assigned to that strategy. Eligible contacts ≥15 years will be offered optional, free, home HIV testing. The primary outcome, proportion of contacts accepting HIV testing, will be assessed by CHWs and analysed using an intention-to-treat approach. Secondary outcomes will be changes in perceived HIV stigma, changes in perceived TB stigma, effects of perceived HIV stigma on HIV test uptake, effects of perceived TB stigma on HIV test uptake and proportions of first-invited contacts who accept HIV testing. Results will inform new, scalable strategies for delivering HIV testing. ETHICS AND DISSEMINATION: This study was approved by the Yale Human Investigation Committee (2000024852), Makerere University School of Public Health Institutional Review Board (661) and Uganda National Council on Science and Technology (HS2567). All participants, including patients and their household contacts, will provide verbal informed consent. Results will be submitted to a peer-reviewed journal and disseminated to national stakeholders, including policy-makers and representatives of affected communities. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT05124665.


Asunto(s)
Infecciones por VIH , Tuberculosis , Infecciones por VIH/diagnóstico , Prueba de VIH , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Estigma Social , Tuberculosis/diagnóstico , Uganda
5.
Front Public Health ; 9: 721952, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34490198

RESUMEN

Background: Contact tracing is a core element of the public health response to emerging infectious diseases including COVID-19. Better understanding the implementation context of contact tracing for pandemics, including individual- and systems-level predictors of success, is critical to preparing for future epidemics. Methods: We carried out a prospective implementation study of an emergency volunteer contact tracing program established in New Haven, Connecticut between April 4 and May 19, 2020. We assessed the yield and timeliness of case and contact outreach in reference to CDC benchmarks, and identified individual and programmatic predictors of successful implementation using multivariable regression models. We synthesized our findings using the RE-AIM implementation framework. Results: Case investigators interviewed only 826 (48%) of 1,705 cases and were unable to reach 545 (32%) because of incomplete information and 334 (20%) who missed or declined repeated outreach calls. Contact notifiers reached just 687 (28%) of 2,437 reported contacts, and were unable to reach 1,597 (66%) with incomplete information and 153 (6%) who missed or declined repeated outreach calls. The median time-to-case-interview was 5 days and time-to-contact-notification 8 days. However, among notified contacts with complete time data, 457 (71%) were reached within 6 days of exposure. The least likely groups to be interviewed were elderly (adjusted relative risk, aRR 0.74, 95% CI 0.61-0.89, p = 0.012, vs. young adult) and Black/African-American cases (aRR 0.88, 95% CI 0.80-0.97, pairwise p = 0.01, vs. Hispanic/Latinx). However, ties between cases and their contacts strongly influenced contact notification success (Intraclass Correlation Coefficient (ICC) 0.60). Surging caseloads and high volunteer turnover (case investigator n = 144, median time from sign-up to retirement from program was 4 weeks) required the program to supplement the volunteer workforce with paid public health nurses. Conclusions: An emergency volunteer-run contact tracing program fell short of CDC benchmarks for time and yield, largely due to difficulty collecting the information required for outreach to cases and contacts. To improve uptake, contact tracing programs must professionalize the workforce; better integrate testing and tracing services; capitalize on positive social influences between cases and contacts; and address racial and age-related disparities through enhanced community engagement.


Asunto(s)
COVID-19 , Trazado de Contacto , Anciano , Humanos , Estudios Prospectivos , Salud Pública , SARS-CoV-2
6.
JMIR Form Res ; 5(10): e31086, 2021 Oct 28.
Artículo en Inglés | MEDLINE | ID: mdl-34586078

RESUMEN

BACKGROUND: Many have proposed the use of Bluetooth technology to help scale up contact tracing for COVID-19. However, much remains unknown about the accuracy of this technology in real-world settings, the attitudes of potential users, and the differences between delivery formats (mobile app vs carriable or wearable devices). OBJECTIVE: We pilot tested 2 separate Bluetooth contact tracing technologies on a university campus to evaluate their sensitivity and specificity, and to learn from the experiences of the participants. METHODS: We used a convergent mixed methods study design, and participants included graduate students and researchers working on a university campus during June and July 2020. We conducted separate 2-week pilot studies for each Bluetooth technology. The first was for a mobile phone app ("app pilot"), and the second was for a small electronic "tag" ("tag pilot"). Participants validated a list of Bluetooth-identified contacts daily and reported additional close contacts not identified by Bluetooth. We used these data to estimate sensitivity and specificity. Participants completed a postparticipation survey regarding appropriateness, usability, acceptability, and adherence, and provided additional feedback via free text. We used tests of proportions to evaluate differences in survey responses between participants from each pilot, paired t tests to measure differences between compatible survey questions, and qualitative analysis to evaluate the survey's free-text responses. RESULTS: Among 25 participants in the app pilot, 53 contact interactions were identified by Bluetooth and an additional 61 by self-report. Among 17 participants in the tag pilot, 171 contact interactions were identified by Bluetooth and an additional 4 by self-report. The tag had significantly higher sensitivity compared with the app (46/49, 94% vs 35/61, 57%; P<.001), as well as higher specificity (120/126, 95% vs 123/141, 87%; P=.02). Most participants felt that Bluetooth contact tracing was appropriate on campus (26/32, 81%), while significantly fewer participants felt that using other technologies, such as GPS or Wi-Fi, was appropriate (17/31, 55%; P=.02). Most participants preferred technology developed and managed by the university rather than a third party (27/32, 84%) and preferred not to have tracing apps on their personal phones (21/32, 66%), due to "concerns with privacy." There were no significant differences in self-reported adherence rates across pilots. CONCLUSIONS: Convenient and carriable Bluetooth technology may improve tracing efficiency while alleviating privacy concerns by shifting data collection away from personal devices. With accuracy comparable to, and in this case, superior to, mobile phone apps, such approaches may be suitable for workplace or school settings with the ability to purchase and maintain physical devices.

7.
J Med Internet Res ; 23(7): e25428, 2021 07 14.
Artículo en Inglés | MEDLINE | ID: mdl-34259640

RESUMEN

BACKGROUND: Harm reduction services reduce the negative consequences of drug injection and are often embedded within syringe service programs (SSPs). However, people who inject drugs (PWID) suboptimally engage with such services because of stigma, fear, transportation restrictions, and limited hours of operation. Mobile health (mHealth) apps may provide an opportunity to overcome these barriers and extend the reach of SSPs beyond that of the traditional brick-and-mortar models. OBJECTIVE: This study aims to assess the prevalence of smartphone ownership, the level of comfort in providing the personal information required to use mHealth apps, and interest in using an mHealth app to access harm reduction services among PWID to guide the development of an app. METHODS: We administered a survey to 115 PWID who were enrolled via respondent-driven sampling from July 2018 to July 2019. We examined the extent to which PWID had access to smartphones; were comfortable in providing personal information such as name, email, and address; and expressed interest in various app-based services. We measured participant characteristics (demographics, health status, and behaviors) and used binary logistic and Poisson regressions to identify independent correlates of mHealth-related variables. The primary regression outcomes included summary scores for access, comfort, and interest. The secondary outcomes included binary survey responses for individual comfort or interest components. RESULTS: Most participants were White (74/105, 70.5%), male (78/115, 67.8%), and middle-aged (mean=41.7 years), and 67.9% (74/109) owned a smartphone. Participants reported high levels of comfort in providing personal information to use an mHealth app, including name (96/109, 88.1%), phone number (92/109, 84.4%), email (85/109, 77.9%), physical address (85/109, 77.9%), and linkage to medical records (72/109, 66.1%). Participants also reported strong interest in app-based services, including medication or sterile syringe delivery (100/110, 90.9%), lab or appointment scheduling (90/110, 81.8%), medication reminders (77/110, 70%), educational material (65/110, 59.1%), and group communication forums (64/110, 58.2%). Most participants were comfortable with the idea of home delivery of syringes (93/109, 85.3%). Homeless participants had lower access to smartphones (adjusted odds ratio [AOR] 0.15, 95% CI 0.05-0.46; P=.001), but no other participant characteristics were associated with primary outcomes. Among secondary outcomes, recent SSP use was positively associated with comfort with the home delivery of syringes (AOR 3.29, 95% CI 1.04-10.3 P=.04), and being older than 50 years was associated with an increased interest in educational materials (AOR 4.64, 95% CI 1.31-16.5; P=.02) and group communication forums (AOR 3.69, 95% CI 1.10-12.4; P=.04). CONCLUSIONS: Our findings suggest that aside from those experiencing homelessness or unstable housing, PWID broadly have access to smartphones, are comfortable with sharing personal information, and express interest in a wide array of services within an app. Given the suboptimal access to and use of SSPs among PWID, an mHealth app has a high potential to address the harm reduction needs of this vulnerable population.


Asunto(s)
Infecciones por VIH , Aplicaciones Móviles , Preparaciones Farmacéuticas , Abuso de Sustancias por Vía Intravenosa , Telemedicina , Reducción del Daño , Humanos , Masculino , Persona de Mediana Edad , Encuestas y Cuestionarios
8.
PLoS One ; 16(5): e0251033, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33951107

RESUMEN

BACKGROUND: Contact tracing is an important tool for suppressing COVID-19 but has been difficult to adapt to the conditions of a public health emergency. This study explored the experiences and perspectives of volunteer contact tracers in order to identify facilitators, challenges, and novel solutions for implementing COVID-19 contact tracing. METHODS: As part of a study to evaluate an emergently established volunteer contact tracing program for COVID-19 in New Haven, Connecticut, April-June 2020, we conducted focus groups with 36 volunteer contact tracers, thematically analyzed the data, and synthesized the findings using the RE-AIM implementation framework. RESULTS: To successfully reach cases and contacts, participants recommended identifying clients' outreach preferences, engaging clients authentically, and addressing sources of mistrust. Participants felt that the effectiveness of successful isolation and quarantine was contingent on minimizing delays in reaching clients and on systematically assessing and addressing their nutritional, financial, and housing needs. They felt that successful adoption of a volunteer-driven contact tracing model depended on the ability to recruit self-motivated contact tracers and provide rapid training and consistent, supportive supervision. Participants noted that implementation could be enhanced with better management tools, such as more engaging interview scripts, user-friendly data management software, and protocols for special situations and populations. They also emphasized the value of coordinating outreach efforts with other involved providers and agencies. Finally, they believed that long-term maintenance of a volunteer-driven program requires monetary or educational incentives to sustain participation. CONCLUSIONS: This is one of the first studies to qualitatively examine implementation of a volunteer-run COVID-19 contact tracing program. Participants identified facilitators, barriers, and potential solutions for improving implementation of COVID-19 contact tracing in this context. These included standardized communication skills training, supportive supervision, and peer networking to improve implementation, as well as greater cooperation with outside agencies, flexible scheduling, and volunteer incentives to promote sustainability.


Asunto(s)
COVID-19/transmisión , Trazado de Contacto , Evaluación de Programas y Proyectos de Salud , Adulto , COVID-19/patología , COVID-19/virología , Femenino , Grupos Focales , Humanos , Entrevistas como Asunto , Masculino , Salud Pública , SARS-CoV-2/aislamiento & purificación , Estados Unidos , Voluntarios/psicología
9.
ACS Sens ; 6(5): 1899-1909, 2021 05 28.
Artículo en Inglés | MEDLINE | ID: mdl-33905237

RESUMEN

Viral fusion is a critical step in the entry pathway of enveloped viruses and remains a viable target for antiviral exploration. The current approaches for studying fusion mechanisms include ensemble fusion assays, high-resolution cryo-TEM, and single-molecule fluorescence-based methods. While these methods have provided invaluable insights into the dynamic events underlying fusion processes, they come with their own limitations. These often include extensive data and image analysis in addition to experimental time and technical requirements. This work proposes the use of the spin-spin T2 relaxation technique as a sensitive bioanalytical method for the rapid quantification of interactions between viral fusion proteins and lipids in real time. In this study, new liposome-coated iron oxide nanosensors (LIONs), which mimic as magnetic-labeled host membranes, are reported to detect minute interactions occurring between the membrane and influenza's fusion glycoprotein, hemagglutinin (HA). The influenza fusion protein's interaction with the LION membrane is detected by measuring changes in the sensitive spin-spin T2 magnetic relaxation time using a bench-top NMR instrument. More data is gleaned from including the fluorescent dye DiI into the LION membrane. In addition, the effects of environmental factors on protein-lipid interaction that affect fusion such as pH, time of incubation, trypsin, and cholesterol were also examined. Furthermore, the efficacy and sensitivity of the spin-spin T2 relaxation assay in quantifying similar protein/lipid interactions with more native configurations of HA were demonstrated using virus-like particles (VLPs). Shorter domains derived from HA were used to start a reductionist path to identify the parts of HA responsible for the NMR changes observed. Finally, the known fusion inhibitor Arbidol was employed in our spin-spin T2 relaxation-based fusion assay to demonstrate the application of LIONs in real-time monitoring of this aspect of fusion for evaluation of potential fusion inhibitors.


Asunto(s)
Gripe Humana , Glicoproteínas Hemaglutininas del Virus de la Influenza , Humanos , Liposomas , Fenómenos Magnéticos
10.
Am J Public Health ; 111(1): 54-57, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33211580

RESUMEN

Contact tracing was one of the core public health strategies implemented during the first months of the COVID-19 pandemic. In this essay, we describe the rapid establishment of a volunteer contact tracing program in New Haven, Connecticut. We describe successes of the program and challenges that were faced. Going forward, contact tracing efforts can best be supported by increased funding to state and local health departments for a stable workforce and use of evidence-based technological innovations.


Asunto(s)
COVID-19/transmisión , Trazado de Contacto , Salud Pública/economía , Voluntarios/educación , Connecticut , Brotes de Enfermedades/prevención & control , Humanos
11.
ACS Infect Dis ; 4(8): 1162-1178, 2018 08 10.
Artículo en Inglés | MEDLINE | ID: mdl-29860830

RESUMEN

Each year, infectious diseases are responsible for millions of deaths, most of which occur in the rural areas of developing countries. Many of the infectious disease diagnostic tools used today require a great deal of time, a laboratory setting, and trained personnel. Due to this, the need for effective point-of-care (POC) diagnostic tools is greatly increasing with an emphasis on affordability, portability, sensitivity, specificity, timeliness, and ease of use. In this Review, we discuss the various diagnostic modalities that have been utilized toward this end and are being further developed to create POC diagnostic technologies, and we focus on potential effectiveness in resource-limited settings. The main modalities discussed herein are optical-, electrochemical-, magnetic-, and colorimetric-based modalities utilized in diagnostic technologies for infectious diseases. Each of these modalities feature pros and cons when considering application in POC settings but, overall, reveal a promising outlook for the future of this field of technological development.


Asunto(s)
Técnicas Biosensibles/métodos , Enfermedades Transmisibles/diagnóstico , Pruebas Diagnósticas de Rutina/métodos , Pruebas en el Punto de Atención , Colorimetría , Técnicas Electroquímicas , Humanos , Fenómenos Magnéticos , Dispositivos Ópticos , Sensibilidad y Especificidad
12.
J Vis Exp ; (127)2017 09 17.
Artículo en Inglés | MEDLINE | ID: mdl-28994755

RESUMEN

Enterohemorrhagic Escherichia coli O157:H7 has been linked to both waterborne and foodborne illnesses, and remains a threat despite the food- and water-screening methods used currently. While conventional bacterial detection methods, such as polymerase chain reaction (PCR) and enzyme-linked immunosorbent assays (ELISA) can specifically detect pathogenic contaminants, they require extensive sample preparation and lengthy waiting periods. In addition, these practices demand sophisticated laboratory instruments and settings, and must be executed by trained professionals. Herein, a protocol is proposed for a simpler diagnostic technique that features the unique combination of magnetic and fluorescent parameters in a nanoparticle-based platform. The proposed multiparametric magneto-fluorescent nanosensors (MFnS) can detect E. coli O157:H7 contamination with as little as 1 colony-forming unit present in solution within less than 1 h. Furthermore, the ability of MFnS to remain highly functional in complex media such as milk and lake water has been verified. Additional specificity assays were also used to demonstrate the ability of MFnS to only detect the specific target bacteria, even in the presence of similar bacterial species. The pairing of magnetic and fluorescent modalities allows for the detection and quantification of pathogen contamination in a wide range of concentrations, exhibiting its high performance in both early- and late-stage contamination detection. The effectiveness, affordability, and portability of the MFnS make them an ideal candidate for point-of-care screening for bacterial contaminants in a wide range of settings, from aquatic reservoirs to commercially packaged foods.


Asunto(s)
Escherichia coli O157/aislamiento & purificación , Colorantes Fluorescentes/química , Microbiología de Alimentos/métodos , Nanopartículas de Magnetita/química , Escherichia coli O157/genética , Magnetismo/métodos
13.
Sci Rep ; 7(1): 7377, 2017 08 07.
Artículo en Inglés | MEDLINE | ID: mdl-28785095

RESUMEN

The aim of this research is twofold: 1) to shed light on zika's binding and entry mechanism while 2) demonstrating the effectiveness of our magnetic relaxation platform to achieve this goal. Magnetic relaxation-sensitive nanoparticles (MRNPs) are used in a novel fashion to analyze binding interactions between the zika envelope protein (ZENV) and proposed host cell receptors: AXL, HSP70, and TIM-1. Computational analysis is also utilized to examine these binding interactions for the first time. In addition, the role of crizotinib as a potential binding inhibitor is demonstrated and the possibility of ligand-independent phosphatidylserine-mediated binding is explored. Our findings suggest that while the extracellular domain of AXL has the highest affinity for ZENV; HSP70, TIM-1, and phosphatidylserine might also play active roles in zika tropism, which offers a potential explanation for the variety of zika-associated symptoms. This is, to our knowledge, the first time that MRNPs have been used to examine and quantify host-zika interactions. Our magnetic relaxation platform allows for timely and sensitive analysis of these intricate binding relationships, and it is easily customizable for further examination of additional host-pathogen interactions.


Asunto(s)
Técnicas Biosensibles , Interacciones Huésped-Patógeno , Nanotecnología , Receptores Virales/metabolismo , Infección por el Virus Zika/metabolismo , Infección por el Virus Zika/virología , Virus Zika/fisiología , Técnicas Biosensibles/métodos , Crizotinib/química , Crizotinib/metabolismo , Compuestos Férricos/química , Humanos , Concentración de Iones de Hidrógeno , Nanopartículas de Magnetita/química , Modelos Biológicos , Modelos Moleculares , Especificidad de Órganos , Fosfatidilserinas/química , Fosfatidilserinas/metabolismo , Conformación Proteica , Proteínas Proto-Oncogénicas/química , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Tirosina Quinasas Receptoras/química , Proteínas Tirosina Quinasas Receptoras/metabolismo , Receptores Virales/química , Temperatura , Acoplamiento Viral , Tirosina Quinasa del Receptor Axl
14.
Mol Pharm ; 14(3): 875-884, 2017 03 06.
Artículo en Inglés | MEDLINE | ID: mdl-28081601

RESUMEN

K-RAS driven non-small-cell lung cancer (NSCLC) represents a major cause of death among smokers. Recently, nanotechnology has introduced novel avenues for the diagnosis and personalized treatment options for cancer. Herein, we report a novel, multifunctional nanoceria platform loaded with a unique combination of two therapeutic drugs, doxorubicin (Doxo) and Hsp90 inhibitor ganetespib (GT), for the diagnosis and effective treatment of NSCLC. We hypothesize that the use of ganetespib synergizes and accelerates the therapeutic efficacy of Doxo via ROS production, while minimizing the potential cardiotoxicity of doxorubicin drug. Polyacrylic acid (PAA)-coated cerium oxide nanoparticles (PNC) were fabricated for the targeted combination therapy of lung cancers. Using "click" chemistry, the surface carboxylic acid groups of nanoceria were decorated with folic acid to target folate-receptor-overexpressing NSCLC. As a result of combination therapy, results showed more than 80% of NSCLC death within 48 h of incubation. These synergistic therapeutic effects were assessed via enhanced ROS, cytotoxicity, apoptosis, and migration assays. Overall, these results indicated that the targeted codelivery of Doxo and GT using nanoceria may offer an alternative combination therapy option for the treatment of undruggable NSCLC.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Cerio/administración & dosificación , Doxorrubicina/farmacología , Proteínas HSP90 de Choque Térmico/antagonistas & inhibidores , Neoplasias Pulmonares/tratamiento farmacológico , Nanopartículas/administración & dosificación , Triazoles/farmacología , Células A549 , Resinas Acrílicas/administración & dosificación , Animales , Apoptosis/efectos de los fármacos , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Línea Celular Tumoral , Terapia Combinada/métodos , Portadores de Fármacos/administración & dosificación , Ácido Fólico/administración & dosificación , Humanos , Neoplasias Pulmonares/metabolismo , Ratas , Especies Reactivas de Oxígeno/metabolismo
16.
ACS Infect Dis ; 2(10): 667-673, 2016 10 14.
Artículo en Inglés | MEDLINE | ID: mdl-27737552

RESUMEN

Enterohemorrhagic Escherichia coli O157:H7 presents a serious threat to human health and sanitation and is a leading cause in many food- and waterborne ailments. While conventional bacterial detection methods such as PCR, fluorescent immunoassays and ELISA exhibit high sensitivity and specificity, they are relatively laborious and require sophisticated instruments. In addition, these methods often demand extensive sample preparation and have lengthy readout times. We propose a simpler and more sensitive diagnostic technique featuring multiparametric magneto-fluorescent nanosensors (MFnS). Through a combination of magnetic relaxation and fluorescence measurements, our nanosensors are able to detect bacterial contamination with concentrations as little as 1 colony-forming unit (CFU). The magnetic relaxation property of our MFnS allow for sensitive screening at low target CFU, which is complemented by fluorescence measurements of higher CFU samples. Together, these qualities allow for the detection and quantification of broad-spectrum contaminations in samples ranging from aquatic reservoirs to commercially produced food.


Asunto(s)
Escherichia coli O157/aislamiento & purificación , Nanopartículas de Magnetita/química , Nanotecnología/métodos , Animales , Bovinos , Recuento de Colonia Microbiana , Escherichia coli O157/crecimiento & desarrollo , Fluorescencia , Lagos/microbiología , Leche/microbiología , Nanotecnología/instrumentación , Sensibilidad y Especificidad
17.
Nanoscale ; 8(47): 19605-19613, 2016 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-27778002

RESUMEN

Rapid detection and diagnosis of pathogenic strains of influenza is necessary for expedited treatment and quicker resolutions to the ever-rising flu pandemics. Considering this, we propose the development of novel magnetic relaxation nanosensors (MRnS) for the rapid detection of influenza through targeted binding with hemagglutinin. 2,6- and 2,3-sialic acid ligands and entry blocker peptides are conjugated to iron oxide nanoparticles to create functional MRnS. Positive detection of various hemagglutinin variants (H1 and H5) is possible with protein concentrations as little as 1.0 nM. Most importantly, detection using functional MRnS is achieved within minutes and differentiates between influenza subtypes. This specificity allows mixtures of MRnS to screen for multiple pathogens at once, discarding the need to conduct multiple individual tests. Current methods used to diagnose influenza, such as RT-PCR and viral culturing, while largely effective, are complex, time-consuming and costly. As well, they are not as sensitive or specific, and have been known to produce false-positive results. In contrast to these methods, targeted MRnS are robust, point-of-care diagnostic tools featuring simple, rapid and low-cost procedures. These qualities, as well as high sensitivity and specificity, and low turnaround times, make a strong case for the diagnostic application of MRnS in clinical settings.


Asunto(s)
Técnicas Biosensibles , Gripe Humana/diagnóstico , Nanopartículas de Magnetita , Nanomedicina , Glicoproteínas Hemaglutininas del Virus de la Influenza/análisis , Humanos , Sensibilidad y Especificidad
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