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BACKGROUND: Angiogenesis is a process that many tumors depend on for growth, development, and metastasis. Vascular endothelial growth factor (VEGF) is one of the major players in tumor angiogenesis in several tumor types, including melanoma. VEGF inhibition is achieved by bevacizumab, a humanized monoclonal antibody that binds with high affinity to VEGF and prevents its function. In order to successfully enable in vivo VEGF expression imaging in a murine melanoma model, we previously labeled bevacizumab with [99mTc]Tc. We observed that this was feasible, but it had prolonged blood circulation and delayed tumor uptake. OBJECTIVE: The aim of this study was to develop a radiolabeled Fab bevacizumab fragment, [99mTc]Tc-HYNICFab( bevacizumab), for non-invasive in vivo VEGF expression molecular imaging. METHODS: Flow cytometry was used to examine VEGF presence in the murine melanoma cell line (B16-F10). Bevacizumab was digested with papain for six hours at 37°C to produce Fab(bevacizumab), which was then conjugated to NHS-HYNIC-Tfa for radiolabeling with [99mTc]Tc. Stability and binding affinity assays were also evaluated. Biodistribution and single photon emission computed tomography/computed tomography (SPECT/CT) were performed at 1, 3, and 6 h (n = 4) after injection of [99mTc]Tc-HYNIC-Fab(Bevacizumab) in normal and B16-F10 tumor-bearing C57Bl/6J mice. RESULTS: Using flow cytometry, it was shown that the B16-F10 murine melanoma cell line has intracellular VEGF expression. Papain incubation resulted in the complete digestion of bevacizumab with good purity and homogeneity. The radiolabeling yield of [99mTc]Tc-HYNIC-Fab(bevacizumab) was 85.00 ± 6.06%, with a specific activity of 291.87 ± 18.84 MBq/mg (n=3), showing in vitro stability. Binding assays demonstrated significant intracellular in vitro VEGF expression. Fast blood clearance and high kidney and tumor uptake were observed in biodistribution and SPECT/CT studies. CONCLUSIONS: We present the development and evaluation of [99mTc]Tc-HYNIC-Fab(bevacizumab), a novel molecular VEGF expression imaging agent that may be used for precision medicine in melanoma and potentially in other VEGF-expressing tumors.
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Environmental exposure to heavy metals and metalloids, originating from sources such as mining and manufacturing activities, has been linked to adverse renal effects. This cross-sectional study assessed children's exposure to these elements and its association with urinary kidney injury molecule-1 (KIM-1). We analyzed data from 99 school-aged children residing in nine localities within the state of Colima, Mexico, during the latter half of 2023. Levels of 23 metals/metalloids and urinary KIM-1 were measured using inductively coupled plasma mass spectrometry (ICP-MS) and enzyme-linked immunosorbent assay, respectively. Detectable levels of these contaminants were found in over 91% of participants, with varied exposure profiles observed across locations ( p = 0.019). After adjusting for confounding factors like gender, age, and locality, higher levels of six metals/metalloids (boron, cadmium, cesium, lithium, selenium, zinc) were significantly associated with increased KIM-1 levels. Tailored mitigation efforts are crucial to protect children from regional pollutant burdens. However, limitations exist, as our study did not capture all potential factors influencing heavy metal/metalloid and KIM-1 levels.
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Exposição Ambiental , Receptor Celular 1 do Vírus da Hepatite A , Metais Pesados , Humanos , Criança , Feminino , Masculino , Estudos Transversais , Receptor Celular 1 do Vírus da Hepatite A/metabolismo , Receptor Celular 1 do Vírus da Hepatite A/análise , Metais Pesados/análise , Metais Pesados/urina , Exposição Ambiental/análise , Exposição Ambiental/efeitos adversos , México , Metaloides/urina , Metaloides/análise , Poluentes Ambientais/análise , Poluentes Ambientais/urina , AdolescenteRESUMO
Sugarcane production has been linked to the release of heavy metals and metalloids (HM/MTs) into the environment, raising concerns about potential health risks. This study aimed to assess the levels of 19 HM/MTs in children living near a sugarcane mill through a pilot biomonitoring investigation. We investigated sex-related differences in these element levels and their correlations. A cross-sectional study was conducted, analyzing data from 20 children in the latter part of 2023. Spearman correlation coefficients with 95% confidence intervals (CIs) were used to assess the relationships between urinary HM/MT levels. Detectable levels of 17 out of the 19 HM/MTs were found across the entire study sample, with arsenic and copper detectable in 95% of the children. Titanium exhibited higher levels in boys compared to girls (p = 0.017). We identified 56 statistically significant correlations, with 51 of them being positive, while the remaining coefficients indicated negative relationships. This study characterized HM/MT levels in school-aged children residing near a sugarcane mill through a pilot biomonitoring investigation. Further research employing larger sample sizes and longitudinal assessments would enhance our understanding of the dynamics and health impacts of HM/MT exposure in this vulnerable population.
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OBJECTIVES: A growing body of research points to a relationship between exposure to migration-related cultural stress and mental health problems. However, such research is often conducted with the tacit assumption that postmigration experiences are the primary-if not singular-driver of psychological distress. In the present study, we aim to extend the cultural-stress paradigm by examining the influences of both premigration crisis exposure and postmigration cultural stress on depression in a sample of Venezuelan crisis migrants in Colombia. METHOD: Survey data for the present study were collected from Venezuelan youth (N = 429, ages 12-17, Mage = 14.0 years, 49% female) and adults (N = 566, ages 18+, Mage = 35.1 years, 82% female) in Bogota and Medellin, Colombia between April and June 2023. RESULTS: Both crisis exposure and discrimination were independently related to depressive symptoms. However, when examined in a multivariate model along with discrimination, crisis exposure was not a significant predictor of depressive symptoms among youth, and its influence weakened considerably among adults. Among both youth and adults, a Crisis Exposure × Discrimination interaction term significantly predicted depressive symptoms, indicating that discrimination was a more robust predictor of depressive symptoms among those endorsing lower levels of crisis exposure than among those reporting high levels of crisis exposure. CONCLUSION: Our research provides new insights into the experiences of Venezuelan migrant youth and adults in Colombia. It provides further support for the importance of drawing from a crisis-informed cultural-stress framework when working with crisis migrant populations. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
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Emerging research provides insights into migration-related cultural stress experiences and mental health among Venezuelan migrants; however, prior studies have not considered the critical distinction between online xenophobia and in-person discrimination. To address this gap, we assess the psychometric properties of an abbreviated version of the Perceived Online Racism Scale (PORS) with Venezuelan migrant youth and examine the interplay between online xenophobia, in-person discrimination, and mental health. Survey data were collected from Venezuelan migrant youth (N = 319; ages 13-17, 49.5% female) in Colombia in April-July 2023. Confirmatory factor analysis (CFA) was used to examine the PORS, and multiple regression was conducted to examine key associations. The CFA showed excellent model fit: χ²(7) = 13.498, p = .061; comparative fit index = .989; Tucker-Lewis index = .977; root-mean-square error of approximation = .055; standardized root-mean-square residual = .026. Controlling for demographic factors, online xenophobia was associated with depressive symptoms (ß = .253, p < .001) and anxiety (ß = .200, p = .001). The online xenophobia-mental health association weakened when controlling for in-person discrimination but remained nevertheless significant (depression: ß = .181, p = .002, anxiety: ß = .135, p = .026). Interaction effects (Online × In-Person) revealed a pattern in which greater exposure to online xenophobia was associated with greater distress, but only at relatively low levels of in-person discrimination. Findings provide new insights regarding (a) the properties of an increasingly relevant measure of cultural stress, (b) how online xenophobia relates to mental health, and (c) the interplay of online and in-person cultural stressors vis-à-vis mental health among Venezuelan migrant youth. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
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Hurricane María caused significant devastation on the island of Puerto Rico, impacting thousands of lives. Puerto Rican crisis migrant families faced stress related to displacement and relocation (cultural stress), often exhibited mental health symptoms, and experienced distress at the family level. Although cultural stress has been examined as an individual experience, little work has focused on the experience as a family. To address this gap, we conducted a mixed-methods study designed to examine the predictive effects of cultural stress on family conflict and its mental health implications among Puerto Rican Hurricane María parent and child dyads living on the U.S. mainland. In the quantitative phase of the study, 110 parent-child dyads completed an online survey assessing cultural stress, family dynamics, and mental health. As part of our primary analysis, we estimated a structural equation path model. Findings from the quantitative phase showed a significant positive relationship between family cultural stress and family conflict, as well as individual parent and child mental health symptoms. In the qualitative phase of the study, 35 parent-child dyads participated in individual interviews. Findings from the interviews revealed variations in difficulties related to language, discrimination, and financial burdens, with some participants adapting more quickly and experiencing fewer stressors. Findings also highlight the impact on mental health for both parents and youth, emphasizing the family-level nature of cultural stress, while noting a potential discrepancy between qualitative and quantitative findings in the discussion of family conflict.
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Saúde Mental , Estresse Psicológico , Humanos , Porto Rico/etnologia , Feminino , Masculino , Estresse Psicológico/etnologia , Estresse Psicológico/psicologia , Adulto , Criança , Saúde Mental/etnologia , Tempestades Ciclônicas , Hispânico ou Latino/psicologia , Conflito Familiar/psicologia , Conflito Familiar/etnologia , Refugiados/psicologia , Pessoa de Meia-Idade , Relações Familiares/psicologia , Relações Familiares/etnologia , AdolescenteRESUMO
Key Clinical Message: The increased life expectancy in patients with hemophilia (PwH) over the last years has raised the incidence of comorbidities, including thromboembolic events. Thromboembolic events are rare in PwH and most of them occur in the presence of exogenous risk factors. There is still scarce scientific evidence on the optimal antithrombotic treatment and management approach in this population. Abstract: In the hemophilic population thromboembolic events are rare. Most of them are often multifactorial and occur in the presence of both exogenous (orthopedic surgery, intensive replacement therapy, use of central venous catheters ) and endogenous (cardiovascular diseases) risk factors. We describe the case of a 43-year-old patient with severe hemophilia B (sHB) receiving prophylaxis with eftrenonacog alfa (rFIXFc) and antithrombotic treatment due to portal vein thrombosis. The patient was treated with extended half- life factor IX (EHL-FIX) prophylaxis maintaining higher trough levels to avoid new bleeding episodes associated to the underlying disease and the use of antithrombotic therapy with low molecular weight heparin. EHL-FIX concentrates allow prolonged intervals between intravenous infusions and higher hemostatic protection thanks to increased factor trough levels. This current case report provides clinical evidence in antithrombotic management in a patient with severe hemophilia B.
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On September 20, 2017, Hurricane Maria made landfall in Puerto Rico, devastating the archipelago and forcing thousands of Puerto Ricans to migrate to the U.S. mainland. Guided by a cultural stress theory framework, the present mixed method study examined how various cultural stressors impact participants' daily interactions and mental health outcomes. A total of 319 adult Hurricane Maria survivors residing on the U.S. mainland participated in the study. A mixed method sequential explanatory design was used. First, we used latent profile analysis (LPA) and multinomial logistic regression to identify the varied cultural stress experiences that participants had. Then we used data from semistructured interviews to better understand the experiences of participants classified into the different LPA profiles. Four profiles were identified: "moderate cultural stress" (35%), "overall low" (29%), "high cultural stress" (26%), and "low language stress" (10%). Multinomial regression indicated that members of the moderate cultural stress, high cultural stress, and low language stress profiles all reported significantly higher depressive and anxiety symptoms compared to members of the overall low profile. Qualitative data exemplified the daily experiences of participants placed into each profile, demonstrating that participants have rich and varied experiences that can contribute to their mental health symptoms. The present study documents the contributions of hurricane trauma and cultural stress vis-à-vis current mental health symptoms. Clinicians working with Hurricane Maria survivors should be cognizant of and inquire about migration-related cultural stressors including discrimination, feelings of being unwelcomed, and difficulty communicating in the destination community's dominant language. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
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Anxiety is the most prevalent mental health disorder among adults worldwide. Given its increased prevalence among migrants due to their marginalized position in the societies where they reside, psychometric evaluations of anxiety measures such as the Generalized Anxiety Disorder-7 (GAD-7) are needed for use with migrants. The present study is the first attempt to compare the structure of GAD-7 scores for (a) different Latino groups in the same country and (b) the same Latino group in two different countries. Using three samples of Mexican and Venezuelan migrants (total N = 933), we provide reliability and validity evidence of the GAD-7 for use with adult Latino migrants. Utilizing confirmatory factor analysis and item response theory, we demonstrate that the GAD-7 is internally consistent, possesses a strong single-factor structure, and generates scores with equivalent psychometric properties. GAD-7 is appropriate for use with Mexican and Venezuelan migrants across differing gender groups and education levels.
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Fluid status (FS) is a diagnostic challenge in critically ill patients with COVID-19. Here, we compared parameters related to FS derived from cumulative fluid balance (CFB), bioelectrical impedance analysis (BIA) and venous congestion assessed by ultrasound (VExUS) to predict mortality. We retrospectively reviewed the medical records of individuals with severe pneumonia due to COVID-19 between July and November 2021 in a single center. Comorbidities, demographic, clinical and laboratory data as well as results from CFB, BIA and VExUS measurements were collected on admission and weekly afterwards for two consecutive evaluations. Seventy-nine patients were included, of which eighteen (14.2%) died. Abnormalities of FS were only identified by BIA. Extracellular water/total body water ratio (ECW/TBW) > 0.394 (overhydrated) by BIA was a good predictor of mortality (AUC = 0.78, 95% CI: 0.067-0.89). Mortality risk was higher in overhydrated patients (OR: 6.2, 95% CI: 1.2-32.6, p = 0.02) and in persistently overhydrated patients (OR: 9.57, 95% CI: 1.18-77.5, p = 0.03) even after adjustment to age, serum albumin and acute kidney injury (AKI) in stages 2-3. Time to death was shorter in overhydrated patients (HR: 2.82, 95% CI: 1.05-7.5, log-rank test p = 0.03). Abnormalities in FS associated with mortality were only identified by BIA in critically ill patients with COVID-19.
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Aim: ChiTn, a mouse/human chimeric anti-Tn monoclonal antibody, was radiolabeled with iodine-131 (131I) and technetium-99m (99mTc) to assess its biodistribution and internalization in Tn-expressing (Tn+) and wild-type (Tn-) LL/2 lung cancer cells. Results: Selective accumulation and gradual internalization of ChiTn were observed in Tn+ cells. Biodistribution in mice with both Tn+ or Tn- lung tumors indicated that the uptake of radiolabeled ChiTn within tumors increased over time. Dual-labeling experiments with 99mTc and 131I showed different biodistribution patterns, with 99mTc exhibiting higher values in the liver, spleen, and kidneys, while 131I showed higher uptake in the thyroid and stomach. However, tumor uptake did not significantly differ between Tn+ and Tn- tumors. To improve tumor targeting, Losartan, an antihypertensive drug known to enhance tumor perfusion and drug delivery, was investigated. Biodistribution studies in Losartan-treated mice revealed significantly higher radiolabeled ChiTn uptake in Tn+ tumors. No significant changes were observed in the uptake of the control molecule IgG-HYNIC™99mTc. Conclusions: These findings demonstrate the enhanced tumor targeting of radiolabeled ChiTn in Losartan-treated mice with Tn-expressing lung tumors. They highlight the potential of ChiTn as a theranostic agent for cancer treatment and emphasize the importance of Losartan as an adjunctive treatment to improve tumor perfusion and drug delivery.
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Anticorpos Monoclonais , Radioisótopos do Iodo , Losartan , Neoplasias Pulmonares , Animais , Camundongos , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Losartan/farmacologia , Losartan/farmacocinética , Losartan/administração & dosagem , Distribuição Tecidual , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/farmacocinética , Tecnécio , Compostos Radiofarmacêuticos/farmacocinética , Compostos Radiofarmacêuticos/farmacologia , Linhagem Celular Tumoral , Feminino , Proteína Tumoral 1 Controlada por TraduçãoRESUMO
Abstract The goal of this work is to identify new fatty acid-mimetic 99mTc-complexes to be used as myocardial imaging agents that allow studying heart abnormalities in high-risk patients. In this sense, we designed a fatty acid-mimetic substructure including an amide moiety that, among other properties, could improve myocardial residence time. A diamide with a chain length of 15 atoms and porting a 6-hydrazinonicotinyl (HYNIC) chelator, and an analog with a short carbon-chain, were prepared with convergent organic synthetic procedures and radiolabeled with 99mTc using tricine as the sole coligand. The in vivo proofs of concept were performed using healthy mice. The new 99mTc-complexes were obtained with adequate radiochemical purity. The lipophilicities were in agreement with the length of the chains. While both 99mTc-complexes showed uptake in the myocardial muscle, the designed radiopharmaceutical with the longest chain length had preferential target-uptake and target-retention compared to other complexes described in the bibliography. Further studies, involving imaging assays, synthetic modifications, and assay of new coligands for 99mTc-HYNIC complexes, are currently ongoing.
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Animais , Feminino , Camundongos , Compostos Radiofarmacêuticos/efeitos adversos , Ácidos Graxos/agonistas , Amidas/efeitos adversos , Cardiopatias Congênitas/classificaçãoRESUMO
Introduction: The asbestos industry began its operations in Colombia in 1942 with the establishment of an asbestos-cement facility in Sibaté, located in the Department of Cundinamarca. Despite extensive asbestos use and production in Colombia, the country lacks a reliable epidemiological surveillance system to monitor the health effects of asbestos exposure. The Colombian health information system, known as SISPRO, did not report mesothelioma cases diagnosed in the municipality, posing a significant challenge in understanding the health impacts of asbestos exposure on the population of Sibaté. Methods: To address this issue, an active surveillance strategy was implemented in Sibaté. This strategy involved conducting door-to-door health and socioeconomic structured interviews to identify Asbestos-Related Diseases (ARDs). Validation strategies included a thorough review of medical records by a panel of physicians, and the findings were communicated to local, regional, and national authorities, as well as the general population. Results: The active surveillance strategy successfully identified a mesothelioma cluster in Sibaté, revealing the inadequacy of the existing health information system in monitoring asbestos-related diseases. The discovery of this cluster underscores the critical importance of implementing active surveillance strategies in Colombia, where governmental institutions and resources are often limited. Conclusion: The findings of this study emphasize the urgent need for Colombia to establish a reliable epidemiological surveillance system for asbestos-related diseases (ARDs). Active surveillance strategies can play a crucial role in identifying mesothelioma clusters and enhancing our understanding of the health effects of asbestos exposure in low- and middle-income countries.
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Amianto , Mesotelioma Maligno , Mesotelioma , Exposição Ocupacional , Síndrome do Desconforto Respiratório , Humanos , Colômbia/epidemiologia , Países em Desenvolvimento , Exposição Ocupacional/efeitos adversos , Mesotelioma/epidemiologiaRESUMO
INTRODUCTION: Acute retinal necrosis (ARN) is a severe eye disease demanding swift treatment to prevent blindness. Early action involving antiviral medications and corticosteroids is crucial for optimal visual outcomes. OBJECTIVE: We present an ARN case series showcasing treatment experience and results. METHODOLOGY: Patients diagnosed with ARN based on SUN Working Group 2021 criteria were included; all underwent comprehensive eye exams, PCR analysis, and imaging. RESULTS: Eight patients were studied; PCR confirmed ARN in six. Induction treatment, either oral valacyclovir (5/8) or intravenous acyclovir (3/8), lasted 10-14 days. Maintenance included oral valacyclovir (6/8), oral valganciclovir (2/8) for six months, along with intravitreal ganciclovir. Visual outcomes were similar for oral and intravenous therapies; poor baseline acuity and macular involvement tend to result in a worse final acuity. CONCLUSIONS: Swift treatment is vital to ARN management. Our findings emphasize effective treatment strategies' role in visual prognosis. ABBREVIATIONS: ACV: Acyclovir; BCVA: Best Corrected Visual Acuity; CMV: Cytomegalovirus; EBV: Epstein Barr Virus; FTA-ABS: Fluorescent treponemal antibody absorption test; HSV 1-2: Herpes simplex virus 1-2; HIV: Human Immunodeficiency Virus; IV-ACV: Intravenous- Acyclovir; PCR: Polymerase Chain Reaction;Tg: Toxoplasma gondii; VZV: Varicella Zoster Virus; VCV: Valacyclovir; VDRL: Venereal disease research laboratory test.
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INTRODUCTION: Rare bleeding disorders (RBD) constitute 5% of total hereditary bleeding disorders, although the number could be higher, due to the presence of undiagnosed asymptomatic patients. The objective of this study was to analyze the prevalence and characteristics of patients with severe RBDs in our area. MATERIAL AND METHODS: We analyzed the patients with RBD followed at a tertiary-level hospital between January 2014 and December 2021. RESULTS: A total of 101 patients were analyzed, with a median age at diagnosis of 27.67 years (range 0-89), of which 52.47% were male. The most frequent RBD in our population was FVII deficiency. Regarding the diagnostic reason, the most frequent cause was a preoperative test and only 14.8% reported bleeding symptoms at the time of diagnosis. A genetic study was carried out in 63.36% of patients and the most frequent mutation type found was finding a missense mutation. CONCLUSIONS: The distribution of RBDs in our centre is similar to the one reported in the literature. The majority of RBDs were diagnosed from a preoperative test and this allowed preventive treatment prior to invasive procedures to avoid bleeding complications. 83% of patients did not have a pathological bleeding phenotype according to ISTH-BAT.
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Introducción: el mieloma múltiple es un trastorno hematológico maligno y el segundo cáncer de la sangre más frecuente. El proceso de la angiogénesis tumoral es fundamental para el crecimiento y metástasis de muchos tipos de tumores, incluido en mieloma múltiple. Se sabe que la sobreexpresión del factor de crecimiento endothelial vascular se encuentra asociado a un mal pronóstico en esta patología, representando un blanco clave para la terapia anti-angiogénica en mieloma múltiple. El anticuerpo monoclonal Bevacizumab es capaz de unirse con gran afinidad al factor de crecimiento endothelial vascular bloqueando su acción. Objetivo: evaluar el Fab(Bevacizumab) marcado con 99mTc o Cy7 como potenciales agentes de imagen moleculares de la expresión de factor de crecimiento endothelial vascular en mieloma múltiple. Material y métodos: la expresión de factor de crecimiento endothelial vascular fue analizada mediante citometría de flujo en la línea celular huaman de mieloma múltiple, la MM1S. Fab(Bevacizumab) fue producido mediante digestión de Bevacizumab con papaína, conjugado a NHS-HYNIC-Tfa y radiomarcado con 99mTc. Se realizaron estudios de biodistribución y de tomografía computarizada por emisión del fotón simple. A su vez, Fab(Bevacizumab) fue marcado con Cy7 para obtener imágenes de fluorescencia in vivo hasta 96 horas. Resultados: el análisis por citometría de flujo en la línea celular MM1S reveló que la expresión de factor de crecimiento endothelial vascular es predominantemente intracelular. Los estudios de biodistribución y SPECT/CT del complejo 99mTc-HYNIC-Fab(Bevacizumab) mostraron una rápida eliminación sanguínea y una significativa captación a nivel renal y tumoral. Las imágenes por fluorescencia empleando Cy7-Fab(Bevacizumab) permitieron la visualización tumoral hasta 96 h p.i. Conclusiones: logramos visualizar la expresión de factor de crecimiento endothelial vascular in vivo en mieloma múltiple mediante el empleo del fragmento Fab del anticuerpo anti-VEGF (Bevacizumab) marcado con 99mTc y Cy7. Estos nuevos agentes de imagen molecular podrían ser empleados potencialmente en el ámbito clínico para la estadificación y el seguimiento de pacientes con mieloma múltiple, mediante la visualización radioactiva in vivo de la expresión de factor de crecimiento endothelial vascular en todo el cuerpo. La imagen óptica de estos trazadores mejoraría el muestreo tumoral y podría guiar la extirpación quirúrgica.
Introduction: Multiple myeloma is a hematologic malignancy and the second most common blood cancer. The process of tumor angiogenesis is central to the growth and metastasis of many types of tumors, including multiple myeloma. Overexpression of vascular endothelial growth factor is known to be associated with poor prognosis in this pathology, representing a key target for anti-angiogenic therapy in multiple myeloma. The monoclonal antibody Bevacizumab is able to bind with high affinity to vascular endothelial growth factor blocking its action. Objective: to evaluate 99mTc- or Cy7-labeled Fab(Bevacizumab) as potential molecular imaging agents of vascular endothelial growth factor expression in multiple myeloma. Methods: Vascular endothelial growth factor expression was analyzed by flow cytometry in the multiple myeloma huaman cell line, MM1S. Fab(Bevacizumab) was produced by digestion of Bevacizumab with papain, conjugated to NHS-HYNIC-Tfa and radiolabeled with 99mTc. Biodistribution and single photon emission computed tomography studies were performed. In turn, Fab(Bevacizumab) was labeled with Cy7 to obtain in vivo fluorescence images up to 96 hours. Results: Flow cytometry analysis in the MM1S cell line revealed that vascular endothelial growth factor expression is predominantly intracellular. Biodistribution and SPECT/CT studies of the 99mTc-HYNIC-Fab(Bevacizumab) complex showed rapid blood clearance and significant renal and tumor uptake. Fluorescence imaging using Cy7-Fab(Bevacizumab) allowed tumor visualization up to 96 h p.i. Conclusions: we were able to visualize vascular endothelial growth factor expression in vivo in multiple myeloma using the Fab fragment of the anti-VEGF antibody (Bevacizumab) labeled with 99mTc and Cy7. These new molecular imaging agents could potentially be employed in the clinical setting for staging and monitoring of patients with multiple myeloma by in vivo radioactive visualization of vascular endothelial growth factor expression throughout the body. Optical imaging of these tracers would improve tumor sampling and could guide surgical excision.
Introdução: O mieloma múltiplo é uma malignidade hematológica e o segundo câncer de sangue mais comum. O processo de angiogênese tumoral é fundamental para o crescimento e a metástase de muitos tipos de tumores, incluindo o mieloma múltiplo. Sabe-se que a superexpressão do fator de crescimento endotelial vascular está associada a um prognóstico ruim no mieloma múltiplo, representando um alvo importante para a terapia antiangiogênica no mieloma múltiplo. O anticorpo monoclonal Bevacizumab é capaz de se ligar com alta afinidade ao fator de crescimento endotelial vascular e bloquear sua ação. Objetivo: avaliar o Fab(Bevacizumab) marcado com 99mTc ou Cy7 como possíveis agentes de imagem molecular da expressão do fator de crescimento endotelial vascular no mieloma múltiplo. Métodos: A expressão do fator de crescimento endotelial vascular foi analisada por citometria de fluxo na linha celular de mieloma múltiplo MM1S. O Fab(Bevacizumab) foi produzido pela digestão do Bevacizumab com papaína, conjugado com NHS-HYNIC-Tfa e radiomarcado com 99mTc. Foram realizados estudos de biodistribuição e tomografia computadorizada por emissão de fóton único. Por sua vez, o Fab(Bevacizumab) foi marcado com Cy7 para geração de imagens de fluorescência in vivo por até 96 horas. Resultados: A análise de citometria de fluxo na linha celular MM1S revelou que a expressão do fator de crescimento endotelial vascular é predominantemente intracelular. Os estudos de biodistribuição e SPECT/CT do complexo 99mTc-HYNIC-Fab(Bevacizumab) mostraram uma rápida depuração sanguínea e uma captação renal e tumoral significativa. A imagem de fluorescência usando Cy7-Fab(Bevacizumab) permitiu a visualização do tumor até 96 horas p.i. Conclusões: Conseguimos visualizar a expressão do fator de crescimento endotelial vascular in vivo no mieloma múltiplo usando o fragmento Fab do anticorpo anti-VEGF (Bevacizumab) marcado com 99mTc e Cy7. Esses novos agentes de imagem molecular poderiam ser usados no cenário clínico para o estadiamento e o monitoramento de pacientes com mieloma múltiplo, visualizando radioativamente a expressão do fator de crescimento endotelial vascular in vivo em todo o corpo. A geração de imagens ópticas desses traçadores melhoraria a amostragem do tumor e poderia orientar a excisão cirúrgica.
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Animais , Camundongos , Tecnécio/farmacocinética , Imagem Molecular/métodos , Citometria de Fluxo/métodos , Bevacizumab/farmacocinética , Mieloma Múltiplo/diagnóstico por imagem , Fatores de Crescimento do Endotélio Vascular , Camundongos Endogâmicos BALB CRESUMO
The political climate often changes following the installment of a new president. This volatility presents opportunities for examining how elections might affect vulnerable subgroups such as Hispanic/Latino (HL) adolescents. The present study explored the perception of negative political climate among HL adolescents before and after the 2020 U.S. presidential election and its association with internalizing symptoms and substance use. We conducted the study in Los Angeles and Miami between 2020-2021, with a sample of 304 HL adolescents (Females = 60.8%), aged 15.3 years on average. Participants completed measures of negative political climate (pre- post-election) and measures of depressive symptoms, anxiety, substance misuse, and substance use intentions after the election. We used paired tests and linear mixed-effects modeling to explore changes in perceived negative climate before and after the election. Structural equation modeling was used to determine predictors of negative political climate and its associations with internalizing symptoms and substance use. Results indicated that following the election negative political climate increased significantly in Miami and among Cuban-origin adolescents but not in Los Angeles or among Mexican-origin adolescents. Pre-election perceived negative political climate was significantly predicted by gender, study site, and mother's nativity. Pre-election negative political climate predicted post-election internalizing symptoms and substance use intentions indirectly through post-election negative political climate. HL youth's perceived political climate is a complex construct that might vary across different sociopolitical contexts and populational sub-groups. Exploring variations in politically-based cultural stressors and their role as mental health and substance use risk factors is crucial to addressing HL disparities. KEY WORDS: Adolescence, Hispanic/Latino, political climate, presidential election, internalizing symptoms, substance use.
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Glioblastoma (GBM), as the most central nervous system (CNS) intractable disease, has spoiled millions of lives due to its high mortality. Even though several efforts have been made, the existing treatments have had limited success. In this sense, we studied a lead compound, the boron-rich selective epidermal growth factor receptor (EGFR)-inhibitor hybrid 1, as a potential drug for GBM treatment. For this end, we analyzed the in vitro activity of hybrid 1 in a glioma/primary astrocytes coculture, studying cellular death types triggered by treatment with this compound and its cellular localizations. Additionally, hybrid 1 concentrated boron in glioma cells selectively and more effectively than the boron neutron capture therapy (BNCT)-clinical agent 10B-l-boronophenylalanine and thus displayed a better in vitro-BNCT effect. This encouraged us to analyze hybrid 1 in vivo. Therefore, immunosuppressed mice bearing U87 MG human GBM were treated with both 1 and 1 encapsulated in a modified liposome (recognized by brain-blood barrier peptide transporters), and we observed a potent in vivo per se antitumor activity (tumor size decrease and animal survival increase). These data demonstrate that 1 could be a promising new targeted therapy for GBM.
Assuntos
Terapia por Captura de Nêutron de Boro , Neoplasias Encefálicas , Glioblastoma , Glioma , Camundongos , Humanos , Animais , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/metabolismo , Boro , Compostos de Boro/farmacologia , Compostos de Boro/uso terapêutico , Glioma/tratamento farmacológico , Glioma/radioterapia , Glioma/metabolismo , Glioblastoma/tratamento farmacológicoRESUMO
Resumen Objetivo: Crear la infografía de la guía de alimentación de Dieta Mediterránea Mexicanizada (DMM) y evaluar su comprensión. Material y Métodos: Estudio de tipo descriptivo, el cual constó de dos fases la 1ra. Se creó la infografía de la guía de alimentación de Dieta Mediterránea Mexicanizada. 2da. Se evaluó la apreciación y comprensión de la infografía de la guía de alimentación, en línea a población universitaria, incluidos familiares y conocidos. Resultados: 273 participantes de 42 años promedio, 74% mujeres y 26% varones, más del 94% de los participantes respondió comprender en su totalidad la infografía. DMM es práctica, aplicable, asequible, entendible, buena para el ser humano y ambiente. Conclusión: La Dieta Mediterránea puede prevenir parcial o totalmente el síndrome metabólico, la guía de alimentación de Dieta Mediterránea Mexicanizada promueve una vida sana y bienestar para todas las edades, respalda los objetivos de desarrollo sostenible, será una herramienta de salud pública, práctica, aplicable, asequible, entendible, apta para promoverse en la población mexicana.
Abstract Objective: To create the infographic of the Mexicanized Mediterranean Diet food guide and evaluate its understanding. Material and Methods: Descriptive type study, which consisted of two phases, the 1st. The infographic of the Mexicanized Mediterranean Diet food guide was created. 2nd Appreciation and comprehension of the food guide infographic was evaluated online for the university population, including relatives and acquaintances. Results: 273 participants with an average age of 42, 74% women and 26% men, more than 94% of the participants responded that they understood the infographic in its entirety. DMM is practical, applicable, affordable, understandable, good for humans and the environment. Conclusion: The Mediterranean Diet can partially or totally prevent metabolic syndrome, the Mexicanized Mediterranean Diet food guide promotes a healthy life and well-being for all ages, supports the objectives of sustainable development, will be a practical, applicable public health tool, affordable, understandable, suitable for promotion in the Mexican population.