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1.
J Surg Res ; 296: 281-290, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38301297

RESUMEN

INTRODUCTION: Transportation databases have limited data regarding injury severity of pedestrian versus automobile patients. To identify opportunities to reduce injury severity, transportation and trauma databases were integrated to examine the differences in pedestrian injury severity at street crossings that were signalized crossings (SCs) versus nonsignalized crossings (NSCs). It was hypothesized that trauma database integration would enhance safety analysis and pedestrians struck at NSC would have greater injury severity. METHODS: Single-center retrospective review of all pedestrian versus automobile patients treated at a level 1 trauma center from 2014 to 2018 was performed. Patients were matched to the transportation database by name, gender, and crash date. Google Earth Pro satellite imagery was used to identify SC versus NSC. Injury severity of pedestrians struck at SC was compared to NSC. RESULTS: A total of 512 patients were matched (median age = 41 y [Q1 = 26, Q3 = 55], 74% male). Pedestrians struck at SC (n = 206) had a lower injury severity score (ISS) (median = 9 [4, 14] versus 17 [9, 26], P < 0.001), hospital length of stay (median = 3 [0, 7] versus 6 [1, 15] days, P < 0.001), and mortality (21 [10%] versus 52 [17%], P = 0.04), as compared to those struck at NSC (n = 306). The transportation database had a sensitivity of 63.4% (55.8%-70.4%) and specificity of 63.4% (57.7%-68.9%) for classifying severe injuries (ISS >15). CONCLUSIONS: Pedestrians struck at SC were correlated with a lower ISS and mortality compared to those at NSC. Linkage with the trauma database could increase the transportation database's accuracy of injury severity assessment for nonfatal injuries. Database integration can be used for evidence-based action plans to reduce pedestrian morbidity, such as increasing the number of SC.


Asunto(s)
Peatones , Heridas y Lesiones , Humanos , Masculino , Adulto , Femenino , Accidentes de Tránsito/prevención & control , Transportes , Centros Traumatológicos , Bases de Datos Factuales , Heridas y Lesiones/diagnóstico , Heridas y Lesiones/epidemiología
2.
R I Med J (2013) ; 106(6): 30-34, 2023 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-37368831

RESUMEN

BACKGROUND: Using data from the Rhode Island immunization registry from January 2019 through September 2022, we assessed whether adolescent routine vaccination rates are catching up on losses experienced early in the pandemic. METHODS: For Q1 2020-Q3 2022, we calculated the number of adolescents ages 11-18 receiving a routine vaccine as a percentage of the same quarter in 2019 along with the cumulative difference through Q3 2022. Human papillomavirus (HPV) vaccine trends were further stratified by racial/ethnic identity and by sex. RESULTS: Except for Q1 2021, the number of adolescents receiving each vaccine in each calendar quarter since Q1 2020 was below 100% of the same quarter in 2019, resulting in cumulative "losses" or "deficits" relative to pre-pandemic numbers. CONCLUSIONS: We describe ways Rhode Island can expand on its existing partnerships between primary care providers, public health, and schools to address the decline in adolescent routine vaccination.


Asunto(s)
Infecciones por Papillomavirus , Vacunas contra Papillomavirus , Humanos , Adolescente , Rhode Island , Vacunación , Instituciones Académicas , Infecciones por Papillomavirus/prevención & control
3.
Theranostics ; 13(7): 2057-2071, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37153742

RESUMEN

Purpose: TRA-1-60 (TRA) is an established transcription factor of embryonic signaling and a well-known marker of pluripotency. It has been implicated in tumorigenesis and metastases, is not expressed in differentiated cells, which makes it an appealing biomarker for immunopositron emission tomography (immunoPET) imaging and radiopharmaceutical therapy (RPT). Herein, we explored the clinical implications of TRA in prostate cancer (PCa), examined the potential of TRA-targeted PET to specifically image TRA+ cancer stem cells (CSCs) and assessed response to the selective ablation of PCa CSCs using TRA-targeted RPT. Experimental Design: First, we assessed the relationship between TRA (PODXL) copy number alterations (CNA) and survival using publicly available patient databases. The anti-TRA antibody, Bstrongomab, was radiolabeled with Zr-89 or Lu-177 for immunoPET imaging and RPT in PCa xenografts. Radiosensitive tissues were collected to assess radiotoxicity while excised tumors were examined for pathologic treatment response. Results: Patients with tumors having high PODXL CNA exhibited poorer progression-free survival than those with low PODXL, suggesting that it plays an important role in tumor aggressiveness. TRA-targeted immunoPET imaging specifically imaged CSCs in DU-145 xenografts. Tumors treated with TRA RPT exhibited delayed growth and decreased proliferative activity, marked by Ki-67 immunohistochemistry. Aside from minor weight loss in select animals, no significant signs of radiotoxicity were observed in the kidneys or livers. Conclusions: We successfully demonstrated the clinical significance of TRA expression in human PCa, engineered and tested radiotheranostic agents to image and treat TRA+ prostate CSCs. Ablation of TRA+ CSCs blunted PCa growth. Future studies combining CSC ablation with standard treatment will be explored to achieve durable responses.


Asunto(s)
Células Madre Pluripotentes , Neoplasias de la Próstata , Masculino , Animales , Humanos , Radioisótopos , Circonio , Tomografía Computarizada por Rayos X , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/metabolismo , Radiofármacos , Células Madre Pluripotentes/metabolismo , Línea Celular Tumoral
4.
Am J Obstet Gynecol MFM ; 4(6): 100698, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-35908729

RESUMEN

BACKGROUND: Rates of vaginal birth after cesarean delivery have decreased and cesarean delivery rates have increased in the last 2 decades. Evidence on short-term neonatal outcomes is available, but data on long-term childhood outcomes following vaginal birth after cesarean delivery are insufficient. Long-term childhood outcome data are essential in decision-making regarding mode of delivery. OBJECTIVE: This study aimed to evaluate the association between delivery mode and long-term educational outcomes of the children of pregnant individuals with a previous cesarean delivery. STUDY DESIGN: This was a retrospective cohort study linking Rhode Island third-grade education data from 2014 to 2017 to birth certificate data. Data were obtained from a statewide database using Department of Education data, and were linked to Department of Health birth certificate data. Participants were children of multiparous women who were term, singleton births without congenital anomalies. Children delivered by primary cesarean delivery were excluded. The exposure was mode of delivery classified as vaginal birth after cesarean delivery, repeated cesarean delivery, or repeated vaginal birth. The primary outcome was children's third-grade reading and math proficiency. Bivariate analyses were conducted to assess differences in demographic variables. Bivariable and multivariable log-binomial regression was used to examine the association between subject proficiency and predictors including mode of delivery, maternal education, sex, child race or ethnicity, and lunch subsidy. RESULTS: Of the 10,923 children who met the inclusion criteria, 2.0% were delivered by vaginal birth after cesarean delivery, 22.0% by repeated cesarean delivery, and 76.0% by repeated vaginal delivery. After adjustment for confounders, there was no difference in reading proficiency (adjusted risk ratio, 0.98; 95% confidence interval, 0.84-1.15) or math proficiency (adjusted risk ratio, 0.99; 95% confidence interval, 0.84-1.15) between those born by vaginal birth after cesarean delivery and those born by repeated cesarean delivery. There was no difference found in either proficiency between children born by repeated vaginal birth and those born by repeated cesarean delivery (reading: adjusted risk ratio, 0.97; 95% confidence interval, 0.93-1.01; math: adjusted risk ratio, 0.97; 95% confidence interval, 0.92-1.02). CONCLUSION: In comparison with repeated cesarean delivery, both vaginal birth after cesarean delivery and repeated vaginal birth were not associated with differences in educational outcomes. This may aid in counseling about long-term safety outcomes regarding vaginal birth after cesarean delivery and may assist in shared decision-making when selecting between trial of labor after cesarean delivery and repeated cesarean delivery.


Asunto(s)
Trabajo de Parto , Parto Vaginal Después de Cesárea , Preescolar , Embarazo , Recién Nacido , Humanos , Niño , Femenino , Parto Vaginal Después de Cesárea/efectos adversos , Estudios Retrospectivos , Cesárea/efectos adversos , Parto Obstétrico
5.
AIDS Behav ; 26(11): 3761-3774, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35661018

RESUMEN

Intimate partner violence (IPV) has been implicated in HIV acquisition and worse HIV outcomes. Limited research focuses on the experiences of Black gay and bisexual men. Using data from cross-sectional surveys in Baltimore, Maryland, and Jackson, Mississippi, we analyzed the association between IPV victimization and HIV-related outcomes among 629 adult Black gay and bisexual men, among whom 53% self-reported a negative result at last HIV test. 40% of participants reported lifetime physical, sexual, and/or psychological IPV victimization, and 24% past-year victimization. Recent and lifetime IPV were associated with recent clinical diagnosis of STI (adjPrR: 1.44; 95%CI: 1.08-1.92) and ART medication interruptions (adjPrR: 1.59; 95%CI: 1.25-2.01), respectively. Physical IPV was inversely associated with current PrEP use (adjPrR: 0.35; 95%CI: 0.13-0.90). Recent IPV was independently correlated with depression symptomatology (adjPrR: 2.36; 95%CI: 1.61-3.47) and hazardous alcohol use (adjPrR: 1.93; 95%CI: 1.42-2.61), with evidence of interactions. IPV-HIV relationships were intersected by internalized stigma, housing instability, poverty, and lack of insurance. Tailored IPV services are urgently needed for comprehensive HIV services for Black gay and bisexual men in the U.S.


Asunto(s)
Infecciones por VIH , Violencia de Pareja , Minorías Sexuales y de Género , Adulto , Estudios Transversales , Infecciones por VIH/epidemiología , Infecciones por VIH/prevención & control , Homosexualidad Masculina/psicología , Humanos , Masculino , Prevalencia , Sindémico , Estados Unidos/epidemiología
6.
AIDS Educ Prev ; 34(1): 69-81, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-35192395

RESUMEN

Pre-exposure prophylaxis (PrEP) is an important and highly effective HIV prevention strategy, but its uptake remains low, particularly among marginalized populations at high risk of HIV. Innovative and community-driven promotion strategies, such as open contests, are needed to address disparities. This directed content analysis uses a PrEP-specific adaptation of the Information-Motivation-Behavioral Skills (IMB) model to identify themes related to PrEP use reflected in community-generated submissions (n = 73) from an open contest conducted to elicit crowdsourced health promotion messages on PrEP in Baltimore, Maryland. In addition to identifying eight of the themes from the adapted IMB model, this analysis also identified two novel salient themes in the motivation category: self-worth/self-love and self-care practice. Findings from this analysis can inform PrEP promotion efforts by pointing to salient themes identified from a community-driven approach that are less well represented in existing research.


Asunto(s)
Fármacos Anti-VIH , Colaboración de las Masas , Infecciones por VIH , Profilaxis Pre-Exposición , Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/prevención & control , Promoción de la Salud , Humanos , Motivación
7.
Community Ment Health J ; 58(4): 624-632, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-34216334

RESUMEN

There is a dearth of research on the intersection of incarceration and psychological distress among men who have sex with men including African American (AAMSM) and Latino MSM (LMSM), populations which bear a large burden of HIV in the U.S. Recent incarceration is an important context to examine psychological distress given the critical implications it has on health outcomes. Using baseline data from the Latino and African American Men's Project (LAAMP), a multi-site randomized HIV behavioral intervention trial, this paper examined the association between previous incarceration within the past three months (i.e., recent incarceration) and psychological distress in the past four weeks, assessed by the Kessler Psychological Distress Scale (K10). Among 1482 AAMSM and LMSM (AAMSM: 911, LMSM: 571), we found 768 (52%) were previously incarcerated, but not in past three months and 138 (9.3%) had been recently incarcerated. After adjusting for race, education, access to resources, current living arrangement, HIV status, and substance use, participants who had been recently incarcerated were more likely to have mild psychological distress i.e., K10 score 20-24 (aRRR:1.43, 95% CI 1.20, 1.71) or severe psychological distress, i.e., K10 score > 30 (aRRR: 1.89, 95% CI 1.22, 2.93) in the past four weeks than those never incarcerated and those previously incarcerated, but not in past three months. Our findings have implications for mental health and HIV prevention services for AAMSM and LMSM with previous incarceration within the past three months.


Asunto(s)
Infecciones por VIH , Distrés Psicológico , Minorías Sexuales y de Género , Negro o Afroamericano/psicología , Infecciones por VIH/epidemiología , Infecciones por VIH/psicología , Hispánicos o Latinos , Homosexualidad Masculina , Humanos , Masculino
8.
Theranostics ; 11(13): 6293-6314, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33995659

RESUMEN

Radioimmunotherapy (RIT) is FDA-approved for the clinical management of liquid malignancies, however, its use for solid malignancies remains a challenge. The putative benefit of RIT lies in selective targeting of antigens expressed on the tumor surface using monoclonal antibodies, to systemically deliver cytotoxic radionuclides. The past several decades yielded dramatic improvements in the quality, quantity, recent commercial availability of alpha-, beta- and Auger Electron-emitting therapeutic radiometals. Investigators have created new or improved existing bifunctional chelators. These bifunctional chelators bind radiometals and can be coupled to antigen-specific antibodies. In this review, we discuss approaches to develop radiometal-based RITs, including the selection of radiometals, chelators and antibody platforms (i.e. full-length, F(ab')2, Fab, minibodies, diabodies, scFv-Fc and nanobodies). We cite examples of the performance of RIT in the clinic, describe challenges to its implementation, and offer insights to address gaps toward translation.


Asunto(s)
Radioinmunoterapia/métodos , Radiofármacos/uso terapéutico , Animales , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/uso terapéutico , Antígenos de Neoplasias/inmunología , Antineoplásicos Inmunológicos/administración & dosificación , Antineoplásicos Inmunológicos/metabolismo , Antineoplásicos Inmunológicos/uso terapéutico , Quelantes/administración & dosificación , Quelantes/metabolismo , Química Clic , Ensayos Clínicos como Asunto , Fraccionamiento de la Dosis de Radiación , Sistemas de Liberación de Medicamentos , Predicción , Humanos , Fragmentos Fab de Inmunoglobulinas/administración & dosificación , Fragmentos Fab de Inmunoglobulinas/uso terapéutico , Linfoma no Hodgkin/radioterapia , Ratones , Terapia Molecular Dirigida , Proteínas de Neoplasias/antagonistas & inhibidores , Neoplasias Experimentales/diagnóstico por imagen , Neoplasias Experimentales/radioterapia , Especificidad de Órganos , Medicina de Precisión , Tolerancia a Radiación , Radiofármacos/administración & dosificación , Proteínas Tirosina Quinasas Receptoras/antagonistas & inhibidores , Anticuerpos de Cadena Única/administración & dosificación , Anticuerpos de Cadena Única/uso terapéutico , Anticuerpos de Dominio Único/administración & dosificación , Anticuerpos de Dominio Único/uso terapéutico , Radioisótopos de Itrio/administración & dosificación , Radioisótopos de Itrio/uso terapéutico
9.
Biochemistry ; 60(21): 1647-1657, 2021 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-34009973

RESUMEN

Tumor susceptibility gene 101 (TSG101) is involved in endosomal maturation and has been implicated in the transcriptional regulation of several steroid hormone receptors, although a detailed characterization of such regulation has yet to be conducted. Here we directly measure binding of TSG101 to one steroid hormone receptor, the glucocorticoid receptor (GR). Using biophysical and cellular assays, we show that the coiled-coil domain of TSG101 (1) binds and folds the disordered N-terminal domain of the GR, (2) upon binding improves the DNA binding of the GR in vitro, and (3) enhances the transcriptional activity of the GR in vivo. Our findings suggest that TSG101 is a bona fide transcriptional co-regulator of the GR and reveal how the underlying thermodynamics affect the function of the GR.


Asunto(s)
Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/fisiología , Complejos de Clasificación Endosomal Requeridos para el Transporte/metabolismo , Complejos de Clasificación Endosomal Requeridos para el Transporte/fisiología , Receptores de Glucocorticoides/metabolismo , Factores de Transcripción/metabolismo , Factores de Transcripción/fisiología , Proteínas de Unión al ADN/genética , Complejos de Clasificación Endosomal Requeridos para el Transporte/genética , Endosomas/metabolismo , Regulación de la Expresión Génica/genética , Regulación de la Expresión Génica/fisiología , Células HeLa , Humanos , Unión Proteica , Dominios Proteicos/fisiología , Elementos Reguladores de la Transcripción/fisiología , Factores de Transcripción/genética , Transcripción Genética/genética , Activación Transcripcional/genética
10.
AIDS Behav ; 25(8): 2325-2335, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-33634354

RESUMEN

Cisgender men who have sex with transgender women face elevated risk for HIV, yet are understudied in prevention research. We conducted in-depth interviews with 19 men who have sex with transgender women in Baltimore, Maryland and Atlanta, Georgia to explore perspectives on HIV prevention. Participants used several strategies to reduce HIV risk: condoms, frequent HIV testing, communication about HIV status with partners, and limiting the types of sex acts performed. While condom use was inconsistent, it was preferred over pre-exposure prophylaxis, in part due to medical distrust. HIV self-testing was generally viewed unfavorably. Although most participants were referred to the study by their transgender women partners, they recommended reaching other men who have sex with transgender women in bars, nightclubs, online, and through social media. HIV prevention interventions should be inclusive of the needs and experiences of men who have sex with transgender women.


Asunto(s)
Infecciones por VIH , Personas Transgénero , Baltimore/epidemiología , Femenino , Georgia/epidemiología , Infecciones por VIH/epidemiología , Infecciones por VIH/prevención & control , Homosexualidad Masculina , Humanos , Masculino
11.
Acad Med ; 96(9): 1259-1262, 2021 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-33570853

RESUMEN

More than 7% of medical students graduate from medical school with at least 1 nonspouse dependent, the majority of whom are likely children. However, there are no national studies on medical students who are parents, and very little is known about what medical schools are doing to support them. A growing literature on the experiences of residents and attending physicians who are parents has neglected to include those of medical students who are parents. It is possible that focusing on research and policy change for residents and attending physicians who are parents without considering medical students may bring about improvements that come too late for many. Further data are needed both on the available policies for students who are parents and on the experiences and needs of these students. Leading national organizations in medical education can help guide medical schools by leveraging their national networks to highlight existing best practices and to foster discussions about how best to support medical students who are parents.


Asunto(s)
Evaluación de Necesidades , Responsabilidad Parental/psicología , Padres/educación , Facultades de Medicina/tendencias , Estudiantes de Medicina/psicología , Niño , Femenino , Humanos , Internado y Residencia/normas , Masculino , Padres/psicología , Médicos Mujeres/psicología , Embarazo , Apoyo Social
12.
J Urban Health ; 97(5): 668-678, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32740700

RESUMEN

Black men who have sex with men (BMSM) bear a disproportionate burden of HIV in the USA. BMSM face stigma, discrimination and barriers to health care access, and utilization. Peers (male or female) may assist BMSM in navigating their health issues by engaging in communication to support in their health care needs. Individuals with high self-efficacy of communicating about men's health issues with peers can be trained as community popular opinion leaders (CPOLs) to change peer behaviors by promoting risk reduction communication. We examined the characteristics associated with high self-efficacy of communicating with peers about men's health issues among 256 BMSM from a behavioral HIV intervention conducted in Baltimore, Maryland. In the multivariate logistic model, gay identity (AOR: 2.10, 95% CI: 1.15,3.83), involvement in the house and ballroom community (AOR: 2.50, 95% CI: 1.14,5.49), larger number of network members who are living with HIV (AOR: 6.34, 95% CI: 1.48,27.11), and larger number of network members who would loan them money (AOR: 1.46, 95% CI: 1.05,2.03) were statistically significantly associated with high self-efficacy of communicating with peers about men's health issues. We also found that having depressive symptoms (AOR: 0.43, 95% CI: 0.24, 0.77) was negatively associated with high self-efficacy of communicating with peers about men's health issues. Findings from the current study can inform future studies to identify better CPOLs who are able to communicate effectively with peers about men's health issues for BMSM.


Asunto(s)
Negro o Afroamericano/psicología , Comunicación , Promoción de la Salud/métodos , Homosexualidad Masculina/psicología , Grupo Paritario , Autoeficacia , Red Social , Adolescente , Adulto , Negro o Afroamericano/estadística & datos numéricos , Anciano , Baltimore , Accesibilidad a los Servicios de Salud , Homosexualidad Masculina/estadística & datos numéricos , Humanos , Relaciones Interpersonales , Masculino , Persona de Mediana Edad , Adulto Joven
13.
J Urban Health ; 97(5): 704-714, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32728845

RESUMEN

Given the importance of spirituality and religion in the lives of many Black gay, bisexual, and other Black sexual minority men (SMM) and the need for additional resources to improve HIV outcomes within this population, research on how spiritual and religious support can promote HIV prevention and treatment among Black SMM is greatly needed. We conducted nine focus groups with 52 spiritual and religious Black SMM in Baltimore, Maryland, to explore opportunities for HIV-related programming that incorporates spiritual and/or religious supports. Thematic analysis of the focus group transcripts was conducted using an iterative constant comparison coding process. Participants expressed a desire for more spiritual/religious support in non-church-based settings and identified the use of peer supports, inclusion of prayer and gospel music, and messaging related to the ideas that God is love, the Bible says to treat yourself preciously, and taking care of your health can strengthen your relationship with God as ways in which this could be incorporated into HIV-related programming. Participants living with HIV identified the message of "keeping the faith" as important for maintaining their HIV treatment plans. Participants also expressed a need for parental supports to improve HIV-related outcomes for Black SMM and potentially expand opportunities for spiritual and religious support to Black SMM within the church. Spirituality and religion can influence HIV outcomes for Black SMM, and the strategies identified by Black SMM in this study could aid in designing culturally congruent HIV prevention and treatment programs situated in the community.


Asunto(s)
Negro o Afroamericano/psicología , Infecciones por VIH/psicología , Homosexualidad Masculina/psicología , Religión , Conducta Sexual/psicología , Espiritualidad , Adulto , Negro o Afroamericano/estadística & datos numéricos , Baltimore/epidemiología , Infecciones por VIH/epidemiología , Homosexualidad Masculina/estadística & datos numéricos , Humanos , Masculino , Adulto Joven
14.
Front Immunol ; 11: 1067, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32582173

RESUMEN

The past two decades have brought impressive advancements in immune modulation, particularly with the advent of both cancer immunotherapy and biologic therapeutics for inflammatory conditions. However, the dynamic nature of the immune response often complicates the assessment of therapeutic outcomes. Innovative imaging technologies are designed to bridge this gap and allow non-invasive visualization of immune cell presence and/or function in real time. A variety of anatomical and molecular imaging modalities have been applied for this purpose, with each option providing specific advantages and drawbacks. Anatomical methods including magnetic resonance imaging (MRI), computed tomography (CT), and ultrasound provide sharp tissue resolution, which can be further enhanced with contrast agents, including super paramagnetic ions (for MRI) or nanobubbles (for ultrasound). Conjugation of the contrast material to an antibody allows for specific targeting of a cell population or protein of interest. Protein platforms including antibodies, cytokines, and receptor ligands are also popular choices as molecular imaging agents for positron emission tomography (PET), single-photon emission computerized tomography (SPECT), scintigraphy, and optical imaging. These tracers are tagged with either a radioisotope or fluorescent molecule for detection of the target. During the design process for immune-monitoring imaging tracers, it is important to consider any potential downstream physiologic impact. Antibodies may deplete the target cell population, trigger or inhibit receptor signaling, or neutralize the normal function(s) of soluble proteins. Alternatively, the use of cytokines or other ligands as tracers may stimulate their respective signaling pathways, even in low concentrations. As in vivo immune imaging is still in its infancy, this review aims to describe the modalities and immunologic targets that have thus far been explored, with the goal of promoting and guiding the future development and application of novel imaging technologies.


Asunto(s)
Sistema Inmunológico/diagnóstico por imagen , Imagen Molecular/métodos , Imagen Óptica/métodos , Animales , Anticuerpos/inmunología , Rastreo Celular , Citocinas/inmunología , Genes Reporteros , Humanos , Sistema Inmunológico/citología , Ligandos , Imagen por Resonancia Magnética , Tomografía de Emisión de Positrones , Radiofármacos , Tomografía Computarizada de Emisión de Fotón Único , Tomografía Computarizada por Rayos X
15.
Mol Pharm ; 17(6): 2099-2108, 2020 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-32330387

RESUMEN

The N-linked biantennary glycans on the heavy chain of immunoglobulin G (IgG) antibodies (mAbs) are instrumental in the recognition of the Fc region by Fc-gamma receptors (FcγR). In the case of full-length mAb-based imaging tracers targeting immune cell populations, these Fc:FcγR interactions can potentially deplete effector cells responsible for tumor clearance. To bypass this problem, we hypothesize that the enzymatic removal of the Fc glycans will disrupt Fc:FcγR interactions and spare tracer-targeted immune cells from depletion during immunopositron emission tomography (immunoPET) imaging. Herein, we compared the in vitro and in vivo properties of 89Zr-radiolabeled CD8-specific murine mAb (anti-CD8wt, clone 2.43), a well-known depleting mAb, and its deglycosylated counterpart (anti-CD8degly). Deglycosylation was achieved via enzymatic treatment with the peptide: N-glycosidase F (PNGaseF). Both anti-CD8wt and anti-CD8degly mAbs were conjugated to p-SCN-Bn-desferrioxamine (DFO) and labeled with 89Zr. Bindings of both DFO-conjugated mAbs to FcγR and CD8+ splenocytes were compared. In vivo imaging and distribution studies were conducted to examine the specificity and pharmacokinetics of the radioimmunoconjugates in tumor-naive and CT26 colorectal tumor-bearing mice. Ex vivo analysis of CD8+ T cell population in spleens and tumors obtained postimaging were measured via flow cytometry and qRT-PCR. The removal of the Fc glycans from anti-CD8wt was confirmed via SDS-PAGE. A reduction in FcγR interaction was exhibited by DFO-anti-CD8degly, while its binding to CD8 remained unchanged. Tissue distribution showed similar pharmacokinetics of [89Zr]Zr-DFO-anti-CD8degly and the wt radioimmunoconjugate. In vivo blocking studies further demonstrated retained specificity of the deglycosylated radiotracer for CD8. From the imaging studies, no difference in accumulation in both spleens and tumors was observed between both radiotracers. Results from the flow cytometry analysis confirmed depletion of CD8+ T cells in spleens of mice administered with DFO-anti-CD8wt, whereas an increase in CD8+ T cells was shown with DFO-anti-CD8degly. No statistically significant difference in tumor infiltrating CD8+ T cells was observed in cohorts administered with the probes when compared to control unmodulated mice. CD8 mRNA levels from excised tumors showed increased transcripts of the antigen in mice administered with [89Zr]Zr-DFO-anti-CD8degly compared to mice imaged with [89Zr]Zr-DFO-anti-CD8wt. In conclusion, the removal of Fc glycans offers a straightforward approach to develop full length antibody-based imaging probes specifically for detecting CD8+ immune molecules with no consequential depletion of their target cell population in peripheral tissues.


Asunto(s)
Linfocitos T CD8-positivos/metabolismo , Animales , Línea Celular , Citometría de Flujo , Humanos , Inmunoconjugados/química , Masculino , Ratones , Ratones Endogámicos BALB C , Tomografía de Emisión de Positrones , Radioquímica
16.
Mol Pharm ; 17(4): 1139-1147, 2020 04 06.
Artículo en Inglés | MEDLINE | ID: mdl-32069422

RESUMEN

TRA-1-60 (TRA) is a cell-surface antigen implicated in drug resistance, relapse, and recurrence. Its expression has been reported in breast, prostate, pancreatic, ovarian tumors, and follicular lymphoma, which paved the development of the therapeutic antibody, Bstrongomab (Bsg), and its drug conjugates. Because patient selection is critical to achieve clinical benefit, a noninvasive imaging agent to select TRA+ lesions in patients is needed. Herein, we report the development of the immunopositron emission tomography (immunoPET) radiotracer 89Zr-radiolabeled Bsg and its potential to delineate TRA+ tumors. Bsg was conjugated to the bifunctional chelator desferrioxamine (DFO) and radiolabeled with [89Zr]Zr-oxalate. [89Zr]Zr-DFO-Bsg was characterized in vitro and evaluated in vivo for uptake and specificity in high and low TRA-expressing BxPC-3 pancreatic and PC-3 prostate cancer models, respectively. Uptake was compared against [89Zr]Zr-DFO-IgG, a nonspecific control radiotracer. Immunohistochemical (IHC) staining of patient cancer tissues using Bsg was performed to explore its clinical significance. A specific activity of 0.18 ± 0.01 GBq/mg (4.8 ± 0.3 mCi/mg) was obtained for [89Zr]Zr-DFO-Bsg. BxPC-3 xenografts exhibited three-fold higher radiotracer uptake compared to [89Zr]Zr-DFO-IgG. Competitive saturation studies using BxPC-3 xenografts further confirmed tracer specificity. The TRA-specific probe had lower accumulation in PC-3 xenografts. Ex vivo autoradiographs correlated with TRA expression from the histopathology of the resected tumor xenografts. Additionally, patient cancer tissues demonstrated positive staining with Bsg with metastatic lesions exhibiting the highest staining. This study demonstrates the potential of [89Zr]Zr-DFO-Bsg as an imaging agent for noninvasive detection of TRA+ tumors.


Asunto(s)
Antígenos de Superficie/metabolismo , Neoplasias Pancreáticas/metabolismo , Neoplasias de la Próstata/metabolismo , Proteoglicanos/metabolismo , Radioisótopos/metabolismo , Circonio/metabolismo , Animales , Línea Celular Tumoral , Quelantes/metabolismo , Deferoxamina/metabolismo , Humanos , Inmunoconjugados/metabolismo , Masculino , Ratones , Ratones Desnudos , Células PC-3 , Tomografía de Emisión de Positrones/métodos
17.
JMIR Res Protoc ; 9(1): e15590, 2020 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-31899456

RESUMEN

BACKGROUND: In the United States, black men who have sex with men (BMSM) are disproportionately affected by HIV. Pre-exposure prophylaxis (PrEP) can reduce HIV incidence. However, real-world implementation of PrEP outside of clinical trials has identified racial disparities in PrEP awareness, uptake, and adherence. In the context of a long history of medical mistrust and power imbalances between scientists and community members, strategies to increase uptake of PrEP among BMSM should consider ways to ensure messages address the needs and priorities of the community. Crowdsourcing contests shift traditional individual tasks to a large group and may enhance community engagement. OBJECTIVE: This paper describes the research protocol of a contest approach to soliciting PrEP promotion messages among BMSM in Baltimore. METHODS: Open-contest implementation and evaluation will proceed as follows: (1) organize a community steering group; (2) develop platforms to solicit crowd input; (3) engage the community to contribute ideas through a Web-based forum and in-person events; (4) evaluate contest entries using both community panel judge assessment and crowd voting; (5) utilize mixed methods to evaluate feasibility, acceptability, and community engagement; and (6) disseminate contest results. RESULTS: This study was funded by the National Institutes of Health (National Institute of Mental Health: R34MH116725) in May 2018 and was approved by the institutional review board in April 2018. The open contest started in February 2019, and data analyses for the mixed method evaluation are expected to complete in December 2019. CONCLUSIONS: The contest will potentially bring new ideas in developing more impactful and locally defined PrEP promotion campaigns. We will determine whether an open-contest approach is acceptable among BMSM in Baltimore. If successful, this study can inform future projects using a similar approach on how to identify and implement programs and policies that are more responsive to community needs and that build up community assets. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/15590.

18.
AIDS Care ; 32(6): 735-743, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-31311286

RESUMEN

Employment status is a key social determinant of health, and many populations in the United States that are impacted by HIV have unequal access to education and employment opportunities which contributes to HIV-related disparities. Black men who have sex with men (BMSM) are one of the groups most heavily burdened by HIV. With improved health outcomes associated with advancements in HIV treatment, research suggests that more people living with HIV want to work. This study describes employment among BMSM living in Baltimore, assesses differences in employment by HIV status and assesses predictors of full-time employment among BMSM. The study found that BMSM have limited access to full-time employment and that this disparity is even more pronounced among BMSM living with HIV. Men living with HIV were less likely to be employed full-time compared to men not living with HIV controlling for education and social contextual factors (OR 0.40 95% CI (0.22-0.73)). HIV will most likely have important implications for employment patterns and trajectories of BMSM over the life course. Additional research is needed among BMSM living with HIV to understand work histories and experiences, facilitating factors, and the impact of various work experiences on the health and wellbeing.


Asunto(s)
Infecciones por VIH , Minorías Sexuales y de Género , Baltimore/epidemiología , Empleo , Homosexualidad Masculina , Humanos , Masculino , Estados Unidos
19.
Cult Health Sex ; 22(10): 1191-1206, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-31594476

RESUMEN

In the USA, Black sexual minority men (BSMM) remain disproportionately impacted upon by HIV and other sexual health issues. Individuals who attend church have lower rates of morbidity and mortality than those that do not; however, church attendance presents a paradox of being protective for some health outcomes and a risk for others among this population. Lesbian, gay, bisexual, and transgender (LGBT) affirming churches may offer support, but little is known about the role of LGBT-affirming churches in the lives of BSMM and how they may impact HIV and other health outcomes. This study explored the role of LGBT-affirming churches in the lives of BSMM. Nine focus groups (N = 52) were conducted in Baltimore City, Maryland between December 2017 and April 2018. Thematic analysis evaluated domains related to how men perceived, experienced, and engaged with LGBT-affirming churches. Three primary themes identified: (1) preferring traditional church environments over LGBT-affirming churches; (2) experiencing the LGBT-affirming church as a space of acceptance, emotional healing, and modelling loving same-sex relationships; and (3) perceiving LGBT-affirming churches as opportunities to engage community members to promote the well-being of BSMM. A secondary theme identified involvement in the house and ballroom community as an LGBT-affirming religious experience.


Asunto(s)
Negro o Afroamericano/estadística & datos numéricos , Promoción de la Salud , Protestantismo , Minorías Sexuales y de Género/psicología , Adulto , Negro o Afroamericano/psicología , Baltimore , Grupos Focales , Humanos , Masculino
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