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ABSTRACT: This study, completed at an sexually transmitted infection (STI) clinic in 2019 to 2020, evaluated patient preferences for telemedicine, express, and standard visits. Active PrEP users preferred telemedicine and express visits, patients with prior STIs preferred express visits, and cisgender women preferred standard visits. Configuring STI clinic visit types requires shared decision making and individualization.
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Infecciones por VIH , Profilaxis Pre-Exposición , Salud Sexual , Enfermedades de Transmisión Sexual , Telemedicina , Humanos , Femenino , Ciudad de Nueva York/epidemiología , Prioridad del Paciente , Enfermedades de Transmisión Sexual/epidemiología , Enfermedades de Transmisión Sexual/prevención & controlRESUMEN
Tertiary lymphoid organs (TLOs) emerge during nonresolving peripheral inflammation, but their impact on disease progression remains unknown. We have found in aged Apoe(-/-) mice that artery TLOs (ATLOs) controlled highly territorialized aorta T cell responses. ATLOs promoted T cell recruitment, primed CD4(+) T cells, generated CD4(+), CD8(+), T regulatory (Treg) effector and central memory cells, converted naive CD4(+) T cells into induced Treg cells, and presented antigen by an unusual set of dendritic cells and B cells. Meanwhile, vascular smooth muscle cell lymphotoxin ß receptors (VSMC-LTßRs) protected against atherosclerosis by maintaining structure, cellularity, and size of ATLOs though VSMC-LTßRs did not affect secondary lymphoid organs: Atherosclerosis was markedly exacerbated in Apoe(-/-)Ltbr(-/-) and to a similar extent in aged Apoe(-/-)Ltbr(fl/fl)Tagln-cre mice. These data support the conclusion that the immune system employs ATLOs to organize aorta T cell homeostasis during aging and that VSMC-LTßRs participate in atherosclerosis protection via ATLOs.
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Envejecimiento/inmunología , Aterosclerosis/inmunología , Receptor beta de Linfotoxina/metabolismo , Miocitos del Músculo Liso/fisiología , Subgrupos de Linfocitos T/inmunología , Linfocitos T Reguladores/inmunología , Adventicia/inmunología , Envejecimiento/genética , Animales , Aorta/patología , Apolipoproteínas E/genética , Aterosclerosis/genética , Diferenciación Celular/genética , Movimiento Celular/genética , Células Cultivadas , Coristoma/inmunología , Memoria Inmunológica , Activación de Linfocitos/genética , Tejido Linfoide/inmunología , Receptor beta de Linfotoxina/genética , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Transgénicos , Proteínas de Microfilamentos/genética , Proteínas Musculares/genéticaRESUMEN
As the COVID-19 pandemic began in 2020, significant public health mitigation efforts were vital to combat an unprecedented health crisis. These efforts, which involved social distancing and self-quarantine, likely worsened a public health crisis of social isolation and loneliness in the U.S., particularly among people with HIV (PWH). Multidisciplinary HIV care centers, which served as the main source of clinical care for PWH and in some cases the only point of social contact, faced evolving dynamics of in-person visits during the COVID-19 pandemic, as well as a shift to telehealth services. Using in-depth interviews, we explored the role that multidisciplinary HIV care centers and providers played in the experience of social isolation among PWH in New York City. We recruited participants (n = 30) from a multidisciplinary HIV care center in NYC between October 2020 and June 2021. We conducted semi-structured interviews to understand the specific domains of social isolation that were mitigated. In this cohort, the major theme that drove both in-person and telehealth care continuity was the strength of the patient-provider relationship. We found that participants saw members of the HIV care center as part of their social network, and providers served both as a source of emotional support and provided important social resources and benefits. Thus, in times of heightened social isolation, HIV care centers can play a critical role in providing social support in addition to clinical care.
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COVID-19 , Infecciones por VIH , SARS-CoV-2 , Aislamiento Social , Telemedicina , Humanos , COVID-19/epidemiología , COVID-19/psicología , Aislamiento Social/psicología , Infecciones por VIH/psicología , Infecciones por VIH/epidemiología , Masculino , Femenino , Ciudad de Nueva York/epidemiología , Adulto , Persona de Mediana Edad , Entrevistas como Asunto , Soledad/psicología , Pandemias , Investigación Cualitativa , Apoyo SocialRESUMEN
The effective prophylaxis and treatment of central nervous system (CNS) involvement in acute lymphoblastic leukaemia (ALL) remains a significant clinical challenge. Developing novel and more effective CNS-directed therapies has been hampered, in part, by our limited understanding of the leukaemia niche in the CNS relative to the bone marrow. Accordingly, defining the molecular and cellular components critical for the establishment and maintenance of the CNS leukaemia niche may lead to new therapeutic opportunities. In prior work we showed that direct intercellular interactions between leukaemia and meningeal cells enhance leukaemia chemoresistance in the CNS. Herein, we show that the CXCR4/CXCL12 chemokine axis contributes to leukaemia-meningeal cell adhesion. Importantly, clinically tested CXCR4 antagonists, which are likely to cross the blood-brain and blood-cerebral spinal fluid barriers and penetrate the CNS, effectively disrupted leukaemia-meningeal cell adhesion. Moreover, by disrupting these intercellular interactions, CXCR4 antagonists attenuated leukaemia chemoresistance in leukaemia-meningeal cell co-culture experiments and enhanced the efficacy of cytarabine in targeting leukaemia cells in the meninges in vivo. This work identifies the CXCR4/CXCL12 axis as an important regulator of intercellular interactions within the CNS leukaemia niche and supports further testing of the therapeutic efficacy of CXCR4 antagonists in overcoming CNS niche-mediated chemoresistance.
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Resistencia a Antineoplásicos , Leucemia , Humanos , Adhesión Celular , Transducción de Señal , Receptores CXCR4/metabolismo , Quimiocina CXCL12/metabolismo , MeningesRESUMEN
Rapid or immediate antiretroviral therapy (iART) after HIV diagnosis improves linkage to care and time to viral suppression. However, iART may affect or be affected by HIV-related stigma and medical mistrust. In this mixed-methods pilot study, we examined the bi-directional role of HIV stigma, medical mistrust, and visit adherence (VA) in the context of iART in a diverse, newly diagnosed patient population. Participants were recruited from an HIV clinic in New York City and we utilized a convergent parallel design integrating quantitative data from demographic surveys, the HIV Stigma Survey (HIVSS), the Medical Mistrust Index (MMI) and electronic medical records, and qualitative data from in-depth interviews. Among the sample (N = 30), 26% (N = 8) initiated ART same-day or within 3 days, while the majority (N = 17) initiated between 4 and 30 days, and 17% (N = 5) initiated ART > 30 days. The median (range) age was 35, and most were English-speaking, Black or Hispanic men and identified as gay. Time to ART initiation was associated with time to linkage to care and time to viral suppression. Day 0-3 group's major theme was iART as stigma prevention, and they had the highest mean HIVSS, lowest MMI score, and a visit adherence of 0.86. Day 4-30 group's major theme was alleviation of internalized stigma, and they had the lowest mean HIVSS score, and highest visit adherence of 0.91. Day > 30 group's major theme was exacerbation of perceived or anticipated stigma, had the highest MMI score and a visit adherence of 0.85. iART implementation requires equitable strategies that address HIV-stigma and mistrust.
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Infecciones por VIH , Retención en el Cuidado , Masculino , Humanos , VIH , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Proyectos Piloto , ConfianzaRESUMEN
Immediate antiretroviral therapy (iART) has been shown to decrease time to viral suppression. Our center underwent significant practice transformation to support iART, including a same-day Open Access (OA) model and enhanced care coordination. We examined whether same-day ART at linkage was associated with favorable proximate and long-term HIV care outcomes. From 2018 to 2019, patients newly diagnosed with HIV, linked to care at our institution, and iART eligible were included. We evaluated the association between iART and time to viral suppression, and between iART and initial/sustained viral suppression and retention in care. We also evaluated the association between use of OA and frequency of care coordination with the same outcomes. Of the 107 patients included, 72 initiated same-day ART at linkage and 35 did not. There was no statistically significant differences in whether patients were ever suppressed, had sustained viral suppression, or were retained in care between those who received same-day ART and those who did not. More care coordination was associated with retention in care (RR 1.21 [1.01-1.5]; p = 0.05). Organizing vital services and ensuring implementation strategies that facilitate iART, while tailoring the approach to the patient's comfort level, is likely optimal for longitudinal HIV care engagement.
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Fármacos Anti-VIH , Infecciones por VIH , Humanos , Infecciones por VIH/diagnóstico , Infecciones por VIH/tratamiento farmacológico , Fármacos Anti-VIH/uso terapéutico , Ciudad de Nueva York/epidemiología , Respuesta Virológica Sostenida , Instituciones de Salud , Carga ViralRESUMEN
BACKGROUND: HIV preexposure prophylaxis (PrEP) remains underutilized despite its efficacy and potential population impact. Achieving PrEP's full potential depends on providers who are knowledgeable and comfortable prescribing it to individuals at risk of acquiring HIV. Previous educational interventions targeting provider-related uptake barriers have had limited success. We designed and tested an electronic medical record (EMR) interpretative comment to improve the delivery of PrEP. METHODS: An EMR comment provided information on PrEP eligibility and referral resources to providers delivering positive chlamydia and gonorrhea results. Positive test results for bacterial sexually transmitted infections before intervention (January 1, 2019-August 23, 2019) and after intervention (August 24, 2019-December 31, 2019) were identified. A retrospective chart review was conducted to ascertain provider documentation of PrEP discussions or provision, HIV prevention discussions, and HIV screening. Pretest-posttest analysis was performed to compare the provision of PrEP and HIV prevention services. RESULTS: We reviewed 856 preintervention encounters spanning 8 months and 461 postencounters spanning 4 months. Patient demographics were comparable. We observed an increase in provider documentation of safe sex and condom counseling (odds ratios [ORs], 1.2 [95% confidence interval {CI}, 1.07-1.18] and 1.11 [95% CI, 1.05-1.17], respectively), and the absence of any HIV prevention discussion decreased (OR, 0.85; 95% CI, 0.80-0.90), but not HIV screening or PrEP documentation. CONCLUSIONS: We demonstrated that an EMR laboratory comment had a modest effect on increasing risk reduction counseling, although not HIV screening or PrEP prescriptions. Future strategies to encourage provider delivery of sexual health services may benefit from more targeted strategies that combine behavioral and information technology approaches.
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Fármacos Anti-VIH , Infecciones por VIH , Profilaxis Pre-Exposición , Centros Médicos Académicos , Consejo , Registros Electrónicos de Salud , Infecciones por VIH/epidemiología , Infecciones por VIH/prevención & control , Humanos , Profilaxis Pre-Exposición/métodos , Estudios Retrospectivos , Sexo Seguro , Consejo SexualRESUMEN
Leukapheresis (LA) in pediatric leukemia is performed for leukostasis, a life-threatening emergency in the setting of extremely increased blast cell counts. The authors aimed to assess the epidemiology of pediatric leukemia who received LA. The authors reviewed US nationally representative admission records of patients less than 20 years of age in the Kids' Inpatient Database for the years 2000, 2003, 2006, 2009, 2012, and 2016. Incidence of new leukemia cases who underwent LA were calculated for the years 2009, 2012, and 2016. Cox and logistic regression analyses were performed to ascertain the risk factors for adverse outcomes. There were 526 admissions for pediatric patients with acute lymphoblastic leukemia (ALL) (n=328), acute myeloid leukemia (AML) (n=124), or chronic myeloid leukemia (CML) (n=74) who underwent LA over the study period. The incidence of leukemia cases that required LA was lower in 2016 than in 2009 or 2012 (1.4%, 2.2%, and 2.7%, respectively; P=0.001). In-hospital mortality was higher in AML than ALL (hzard ratio, 3.2; 95% confidence interval, 1.1-9.1). None with CML died during admission. This first population-based study of LA in pediatric leukemia showed a decreased utilization of LA over recent years. The higher inpatient mortality in AML, as compared with ALL or CML, warrant further investigations.
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Leucemia Mielógena Crónica BCR-ABL Positiva , Leucemia Mieloide Aguda , Leucostasis , Leucemia-Linfoma Linfoblástico de Células Precursoras , Niño , Humanos , Leucaféresis , Leucemia Mielógena Crónica BCR-ABL Positiva/complicaciones , Leucemia Mielógena Crónica BCR-ABL Positiva/epidemiología , Leucemia Mielógena Crónica BCR-ABL Positiva/terapia , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Estudios RetrospectivosRESUMEN
BACKGROUND: Older persons living with HIV (PLWH) need routine healthcare to manage HIV and other comorbidities. This mixed methods study investigated digital equity, constituted as access, use and quality, of HIV and specialty telehealth services for PLWH > 50 years during the initial wave of the COVID-19 pandemic when services transitioned to remote care. METHODS: A survey of closed and open-ended questions was administered to 80 English (N = 63) and Spanish (N = 17) speaking PLWH receiving HIV care at an Academic Medical Center (N = 50) or a Federally Qualified Health Center (N = 30) in New York State. Quantitative analyses examined characteristics predicting telehealth use and visit quality. Qualitative analyses utilized thematic coding to reveal common experiences. Results were integrated to deepen the interpretation. RESULTS: Telehealth access and use were shaped by multiple related and unstable factors including devices and connectivity, technology literacy, and comfort including privacy concerns. Participants demonstrated their substantial effort to achieve the visit. The majority of patients with a telehealth visit perceived it as worse than an in-person visit by describing it as less interpersonal, and resulting in poorer outcomes, particularly participants with less formal education. Technology was not only a barrier to access, but also influenced perceptions of quality. CONCLUSIONS: In the COVID-19 pandemic initial wave, barriers to using telehealth were unequally distributed to those with more significant access and use challenges. Beyond these barriers, examining the components of equity indicate further challenges replicating in-person care using telehealth formats for older PLWH. Work remains to establish telehealth as both equitable and desirable for this population.
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COVID-19 , Infecciones por VIH , Telemedicina , Anciano , Anciano de 80 o más Años , COVID-19/epidemiología , COVID-19/terapia , Infecciones por VIH/epidemiología , Infecciones por VIH/terapia , Humanos , New York/epidemiología , PandemiasRESUMEN
ABSTRACT: Graduate medical training is an opportune time to improve provider delivery of sexually transmitted infection (STI) screening. A survey of trainees found that the majority feel STI screening is their job but identified barriers to successful screening. Training that intentionally address service-specific barriers will be valuable in ending the STI epidemic.
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Enfermedades de Transmisión Sexual , Conocimientos, Actitudes y Práctica en Salud , Humanos , Tamizaje Masivo , Enfermedades de Transmisión Sexual/diagnóstico , Enfermedades de Transmisión Sexual/epidemiología , Enfermedades de Transmisión Sexual/prevención & control , Encuestas y CuestionariosRESUMEN
During the COVID-19 pandemic in New York City, NewYork-Presbyterian Hospital provided HIV prevention patients with gonorrhea/chlamydia testing kits at home. This report describes the program implementation to provide other sexual health clinics with a roadmap in adapting to a "new normal" in providing comprehensive sexual health care virtually to patients.
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COVID-19/epidemiología , Infecciones por VIH/prevención & control , Juego de Reactivos para Diagnóstico , Autoevaluación , Enfermedades de Transmisión Sexual/diagnóstico , Infecciones por Chlamydia/diagnóstico , Infecciones por Chlamydia/epidemiología , Infecciones por Chlamydia/prevención & control , Femenino , Gonorrea/diagnóstico , Gonorrea/epidemiología , Gonorrea/prevención & control , Humanos , Masculino , Ciudad de Nueva York/epidemiología , Enfermedades de Transmisión Sexual/epidemiología , Enfermedades de Transmisión Sexual/prevención & control , Enfermedades de Transmisión Sexual/transmisión , Manejo de Especímenes , Adulto JovenRESUMEN
BACKGROUND: Ending the HIV epidemic requires linkage of at-risk individuals from diverse health care settings to comprehensive HIV prevention services. Sexually transmitted infections (STIs) are significant biomarkers of HIV risk and should trigger preexposure prophylaxis (PrEP) discussion. We reviewed STI testing practices outside of sexual health clinics to identify opportunities for improvement in the provision of HIV prevention services. METHODS: An electronic sexual health dashboard was used to identify patient encounters with a positive gonorrhea, chlamydia, and/or rapid plasma reagin test result between January 1, 2019, and August 23, 2019, at a large urban academic medical center. A retrospective chart review was performed to assess HIV testing, completeness of STI screening, and HIV prevention discussion; inadequate screening was defined as no HIV test in 12 months before STI diagnosis. RESULTS: A total of 815 patients with 856 patient encounters were included. Patients were predominantly female (64.4%); median age was 24 years (range, 18-85 years). The most common test and most common positive test result was the genitourinary gonorrhea/chlamydia nucleic acid amplification test. Multisite testing was rare (7.5% of patient encounters) and performed more frequently in men than in women (20.3% vs. 0.36%). Women were also more likely to be inadequately screened for HIV (15.1% vs. 25.8%).Documentation of PrEP discussion was rare (4.7% of patient encounters) compared with safe sex (44.6%) and condoms (49.8%). Preexposure prophylaxis was discussed almost exclusively with men compared with women (17% vs. 1.1%). CONCLUSIONS: In patients diagnosed with bacterial STI outside of sexual health clinics, gaps in HIV prevention exist. HIV screening, multisite STI screening, and discussion of PrEP were particularly infrequent among women.
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Gonorrea , Infecciones por VIH , Profilaxis Pre-Exposición , Enfermedades de Transmisión Sexual , Adulto , Femenino , Gonorrea/diagnóstico , Gonorrea/epidemiología , Gonorrea/prevención & control , Infecciones por VIH/diagnóstico , Infecciones por VIH/prevención & control , Humanos , Masculino , Estudios Retrospectivos , Enfermedades de Transmisión Sexual/diagnóstico , Enfermedades de Transmisión Sexual/epidemiología , Enfermedades de Transmisión Sexual/prevención & control , Adulto JovenRESUMEN
Epstein-Barr virus-positive diffuse large B-cell lymphoma (EBV+ DLBCL) in pediatrics most commonly occurs as an iatrogenic immunodeficiency-associated lymphoproliferative disease. We report an 18-year-old female individual with refractory systemic juvenile idiopathic arthritis, treated with multiple immunosuppressive agents, who was diagnosed with stage III, EBV+ DLBCL. The patient achieved sustained complete remission after 4 weekly doses of rituximab monotherapy and reduction of immunosuppression. This case suggests that a post-transplant lymphoproliferative disease-like treatment approach can be a safe and effective therapy in a nontransplant, yet severely immunosuppressed, patient with EBV+ DLBCL.
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Antineoplásicos Inmunológicos/uso terapéutico , Artritis Juvenil/complicaciones , Infecciones por Virus de Epstein-Barr/complicaciones , Linfoma de Células B Grandes Difuso/complicaciones , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Rituximab/uso terapéutico , Adolescente , Artritis Juvenil/tratamiento farmacológico , Femenino , Humanos , Inmunosupresores/uso terapéutico , Resultado del TratamientoRESUMEN
Respirators are one of the most useful personal protective equipment which can effectively limit the spreading of coronavirus (COVID-19). There are a worldwide shortage of respirators, melt-blown non-woven fabrics, and respirator testing possibilities. An easy and fast filtering efficiency measurement method was developed for testing the filtering materials of respirators. It works with a laser-based particle counting method, and it can determine two types of filtering efficiencies: Particle Filtering Efficiency (PFE) at given particle sizes and Concentration Filtering Efficiency (CFE) in the case of different aerosols. The measurement method was validated with different aerosol concentrations and with etalon respirators. Considerable advantages of our measurement method are simplicity, availability, and the relatively low price compared to the flame-photometer based methods. The ability of the measurement method was tested on ten different types of Chinese KN95 respirators. The quality of these respirators differs much, only two from ten reached 95% filtering efficiency.
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BACKGROUND: Direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV) is highly effective. However, people who inject drugs face significant barriers to DAA access. METHODS: We describe a program that colocates HCV management within a syringe service program in New York City. We performed a retrospective chart review of all patients with confirmed HCV viremia. RESULTS: From 2015 to 2018, 102 patients with viremia completed intake. Fifty-eight patients started DAAs. Nine patients discontinued treatment or were lost to follow-up before completion; 1 is continuing DAA treatment. Of 48 patients who completed therapy, sustained virologic response (SVR) was achieved in 43 (89.6%). Age and established mental health treatment at intake were associated with SVR. Regular cocaine use was negatively associated with SVR in univariate analysis, but this association was not significant after adjustment for age. Of 30 patients completing DAA therapy with active illicit opioid use at intake, 14 (46.4%) engaged in opioid use disorder (OUD) treatment during therapy, and 9 remained in OUD treatment after completion of DAA treatment. CONCLUSIONS: Loss to follow-up is a challenge for people who inject drugs, but among those who completed treatment, SVR was achieved at a high rate. Mental health treatment may facilitate HCV cure. Conversely, HCV therapy may facilitate engagement in OUD treatment and other services.
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Antivirales/uso terapéutico , Hepatitis C/tratamiento farmacológico , Programas de Intercambio de Agujas/organización & administración , Trastornos Relacionados con Opioides/terapia , Cooperación del Paciente/psicología , Abuso de Sustancias por Vía Intravenosa/complicaciones , Adulto , Factores de Edad , Anciano , Consumidores de Drogas/psicología , Consumidores de Drogas/estadística & datos numéricos , Femenino , Hepacivirus/aislamiento & purificación , Hepatitis C/sangre , Hepatitis C/diagnóstico , Hepatitis C/transmisión , Humanos , Masculino , Persona de Mediana Edad , Programas de Intercambio de Agujas/estadística & datos numéricos , Ciudad de Nueva York , Tratamiento de Sustitución de Opiáceos/psicología , Tratamiento de Sustitución de Opiáceos/estadística & datos numéricos , Trastornos Relacionados con Opioides/complicaciones , Cooperación del Paciente/estadística & datos numéricos , Estudios Retrospectivos , Abuso de Sustancias por Vía Intravenosa/prevención & control , Respuesta Virológica Sostenida , Adulto JovenRESUMEN
Central nervous system (CNS) relapse is a common cause of treatment failure in patients with acute lymphoblastic leukaemia (ALL) despite current CNS-directed therapies that are also associated with significant short- and long-term toxicities. Herein, we showed that leukaemia cells exhibit decreased proliferation, elevated reactive oxygen species (ROS) and increased cell death in cerebral spinal fluid (CSF) both in vitro and in vivo. However, interactions between leukaemia and meningeal cells mitigated these adverse effects. This work expands our understanding of the pathophysiology of CNS leukaemia and suggests novel therapeutic approaches for more effectively targeting leukaemia cells in the CNS.
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Meninges/fisiopatología , Leucemia-Linfoma Linfoblástico de Células Precursoras/líquido cefalorraquídeo , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidad , Análisis de SupervivenciaRESUMEN
Protection from acute lymphoblastic leukemia relapse in the central nervous system (CNS) is crucial to survival and quality of life for leukemia patients. Current CNS-directed therapies cause significant toxicities and are only partially effective. Moreover, the impact of the CNS microenvironment on leukemia biology is poorly understood. In this study we showed that leukemia cells associated with the meninges of xenotransplanted mice, or co-cultured with meningeal cells, exhibit enhanced chemoresistance due to effects on both apoptosis balance and quiescence. From a mechanistic standpoint, we found that leukemia chemoresistance is primarily mediated by direct leukemia-meningeal cell interactions and overcome by detaching the leukemia cells from the meninges. Next, we used a co-culture adhesion assay to identify drugs that disrupted leukemia-meningeal adhesion. In addition to identifying several drugs that inhibit canonical cell adhesion targets we found that Me6TREN (Tris[2-(dimethylamino)ethyl]amine), a novel hematopoietic stem cell-mobilizing compound, also disrupted leukemia-meningeal adhesion and enhanced the efficacy of cytarabine in treating CNS leukemia in xenotransplanted mice. This work demonstrates that the meninges exert a critical influence on leukemia chemoresistance, elucidates mechanisms of relapse beyond the well-described role of the blood-brain barrier, and identifies novel therapeutic approaches for overcoming chemoresistance.
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Resistencia a Antineoplásicos , Leucemia , Animales , Sistema Nervioso Central , Citarabina , Humanos , Leucemia/tratamiento farmacológico , Ratones , Calidad de Vida , Microambiente TumoralRESUMEN
The use of nanoparticle reinforced polymer matrices in continuous fiber composites for infrastructure applications requires a comprehensive understanding of viscoelastic creep. Critical parameters affecting the mechanical reinforcement offered by nanoparticles include nanoparticle size and concentration, as well as the interaction between the nanoparticle surface and polymer matrix. Here, we study the viscoelastic creep of nanocomposite systems comprised of glassy thermoplastic polymers and spherical silica nanoparticles of varying sizes and surface functionalization using a dynamic mechanical analysis (DMA) accelerated testing methodology. Significant differences in the nanoparticle dispersions in these nanocomposites were observed via transmission electron microscopy (TEM) and small-angle X-ray scattering (SAXS) and are attributed to differences in the polymer-polymer and polymer-particle interaction strengths. The DMA measurements indicate a decrease in compliance at short times with increased nanoparticle loading that is largely independent of nanoparticle dispersion morphology and polymer-particle interaction strength. Conversely, long term creep behavior shows a much stronger dependence on these parameters with the creep onset time increasing by up to three orders of magnitude. For similar nanoparticle loadings, the time to critical deformation in systems with well-distributed, networked nanoparticle morphologies was larger by an order of magnitude compared to systems exhibiting strong nanoparticle aggregation. The networked systems delayed the time to critical deformation by three orders of magnitude over that of neat polymer. The increase in time to critical deformation is also greater in composites with smaller nanoparticles at similar loadings, which we attribute to the development of percolated nanoparticle networks. These results demonstrate the significant effects polymer-particle interactions and dispersion morphologies can have on the long-term creep compliance of thermoplastic nanocomposites.
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A large-scale eye-tracking study examined individual variability in measures of word recognition during reading among 546 college students, focusing on two established individual-differences measures: the Author Recognition Test (ART) and Rapid Automatized Naming (RAN). ART and RAN were only slightly correlated, suggesting that the two tasks reflect independent cognitive abilities in this large sample of participants. Further, individual variability in ART and RAN scores were related to distinct facets of word-recognition processes. Higher ART scores were associated with increased skipping rates, shorter gaze duration, and reduced effects of word frequency on gaze duration, suggesting that this measure reflects efficiency of basic processes of word recognition during reading. In contrast, faster times on RAN were associated with enhanced foveal-on-parafoveal effects, fewer first-pass regressions, and shorter second-pass reading times, suggesting that this measure reflects efficient coordination of perceptual-motor and attentional processing during reading. These results demonstrate that ART and RAN tasks make independent contributions to predicting variability in word-recognition processes during reading.
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Individualidad , Lectura , Atención , Fóvea Central , HumanosRESUMEN
Most of the commercially available pharmaceutical products for oral administration route are marketed in the tablet dosage forms. However, compression of multiparticulate systems is a challenge for the pharmaceutical research and industry, especially if the individual unit is a coated particle, as the release of the active ingredient depends on the integrity of the coating. In the present study, polymer-coated pellets tableted with different types of excipients (powder, granules, pellets) then were investigated by various tablet-destructive (microscopic) and tablet non-destructive (microfocus X-ray; microCT) imaging methods. The information obtained from the independent evaluation of the in vitro drug release profiles model is confirmed by the results obtained by image analysis, regardless of whether X-ray or stereomicroscopic images of the coated, tableted pellets were used for image analysis. The results of this study show that the novel easy-to-use, fast, and non-destructive MFX method is a good alternative to the already used microscopic image analysis methods regarding the characterization of particulates, compressed into tablets.